2--hydroxy-5-9-dimethyl-2-allyl-6-7-benzomorphan and ketazocine

Evidence from studies which utilise either opiate receptor agonists and antagonists strongly indicate a role for endorphinergic mechanisms in the control of feeding responses. Two means by which these compounds may exert an effect on feeding can be singled-out. Firstly, emerging evidence suggests that the process of achieving satiety (terminating a meal, or choice of a commodity) may be accelerated following treatments with opiate receptor antagonists. Secondly, the preference for highly palatable solutions (sweet solutions have received most attention) in two-bottle tests is blocked after injection of opiate receptor antagonists. This finding has been interpreted in terms of the abolition of the reward or incentive quality associated with the particularly attractive flavour. These two mechanisms of action may represent two aspects of a single, fundamental process. Following an introduction to rat urination model of in vivo kappa agonist activity, the consistent effect of several kappa agonists (including the highly selective U-50,488H) to stimulate food consumption is described. Recognising that members of the dynorphin group of endogenous opioid peptides are kappa receptor ligands, some with a high degree of selectivity, and the evidence the dynorphins and neo-endorphins produce hyperphagia in rats is particularly interesting. Such lines of evidence lead to the hypothesis that peptides of the dynorphin group may act endogenously to promote the expression of normal feeding behaviour.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Benzodiazepines; Benzomorphans; Butorphanol; Choice Behavior; Cyclazocine; Diuresis; Drinking; Dynorphins; Eating; Endorphins; Ethylketocyclazocine; Humans; Morphine; Narcotic Antagonists; Phenazocine; Pyrrolidines; Receptors, Opioid; Receptors, Opioid, kappa; Satiety Response

Topics: Animals; beta-Endorphin; Brain; Cyclazocine; Dogs; Drug Tolerance; Dynorphins; Endorphins; Ethylketocyclazocine; Male; Mice; Morphine; Naloxone; Neuromuscular Junction; Phenazocine; Rabbits; Radioligand Assay; Rats; Receptors, Opioid; Synaptic Transmission

(+)-N-Allylnormetazocine (NANM) binds to at least two sites in the mammalian central nervous system, a high-affinity, haloperidol-sensitive site and a lower-affinity site identified as the phencyclidine (PCP) receptor. The relevance of these sites to the discriminative stimulus properties of (+)-NANM was evaluated in rats trained to discriminate (+)-NANM from saline. Drugs with a high affinity for the haloperidol-sensitive site, including haloperidol, (+)-ketocyclazocine, 1,3-di-ortho-tolyl-guanidine and (-)-butaclamol failed to substitute for the (+)-NANM stimulus. In addition, when they were tested in combination with (+)-NANM, only haloperidol evidenced any antagonistic effects. The antagonistic effects of haloperidol were incomplete and only occurred at doses that substantially disrupted responding. Evidence obtained earlier that (+)-3-(3-hydroxyphenyl)-N-(1-propyl) piperidine could antagonize (+)-NANM was not replicated. On the other hand, PCP-like drugs from diverse chemical classes, including PCP, ketamine, MK-801, (-)-2-methyl-3,3-diphenyl-3-propanolamine, etoxadrol and dextrorphan, all substituted fully for the (+)-NANM stimulus with a potency predicted by their relative potency for PCP-like discriminative stimulus effects and relative affinity for the PCP receptor. Taken together, these results fail to provide evidence for an important role for the high-affinity haloperidol-sensitive binding site for (+)-NANM in its discriminative stimulus properties. Instead, activity at the PCP receptor is predictive of (+)-NANM-like effects.

Topics: Animals; Binding Sites; Butaclamol; Cyclazocine; Discrimination Learning; Ethylketocyclazocine; Haloperidol; Male; Phenazocine; Rats; Rats, Inbred Strains; Receptors, Neurotransmitter; Receptors, Phencyclidine

In vivo and in vitro binding studies, both in whole brain and in selected areas, indicate that non-identical (+)- and (-)-NANM sites exist in the mouse brain, and each exhibits a different regional distribution. The in vivo binding of (+)-3H-NANM was found to be saturable at pharmacologically relevant doses, and represents a relatively small (10-22%) portion of total brain (+)-3H-NANM concentrations. The in vivo binding of (+)-3H-NANM was selectively displaced by (+)-NANM and PCP, and more sensitive to haloperidol and (+)-ketocyclazocine than the (-)-3H-NANM site. The in vivo binding of (-)-3H-NANM was selectively displaced by (-)-NANM, and more sensitive to naloxone and (-) ketocyclazocine than the (+)-3H-NANM site, and insensitive to PCP. This study indicates that the investigation of NANM binding sites is possible using in vivo binding techniques, and that each isomer apparently binds, in the mouse brain, to a single class of distinct sites.

Topics: Animals; Binding, Competitive; Brain; Cyclazocine; Ethylketocyclazocine; Haloperidol; In Vitro Techniques; Mice; Naloxone; Phenazocine; Phencyclidine; Receptors, Opioid; Receptors, sigma; Stereoisomerism

Pigeons were trained to discriminate a dose of either 4.2 mg/kg of U50,488 or 1.0 mg/kg of morphine from water using a two-key drug discrimination procedure. In U50,488-trained pigeons, the kappa agonist bremazocine occasioned drug-appropriate responding during substitution tests, whereas ethylketocyclazocine and ketocyclazocine occasioned intermediate levels of drug-appropriate responding up to and including doses that markedly suppressed response rates. The mu agonists morphine, l-methadone and fentanyl produced responding predominantly on the water-appropriate key. In morphine-trained pigeons, l-methadone, fentanyl, ethylketocyclazocine and ketocyclazocine, but not U50,488 and bremazocine, occasioned drug-appropriate responding. Nonopioid compounds, such as d-amphetamine, pentobarbital, phencyclidine and (+)-SKF 10,047 produced responding predominantly on the water-appropriate key in both U50,488- and morphine-trained pigeons. During tests of antagonism, a 0.1 and 1.0 mg/kg dose of naloxone antagonized completely the discriminative stimulus properties of the training dose of U50,488 and morphine, respectively. In addition, morphine displayed a substantially longer duration of action than U50,488, in that intermediate levels of drug-appropriate responding were evident as long as 4 hr after the administration of morphine and only 1 hr after the administration of U50,488. Over a period of approximately 8 months, the dose-effect curves for the discriminative stimulus properties of both drugs were unchanged. The present findings illustrate further the unique behavioral response of pigeons to the discriminative stimulus properties of the kappa agonists, and establishes that pigeons can discriminate between mu and some kappa agonists.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Columbidae; Cyclazocine; Dextroamphetamine; Discrimination Learning; Dose-Response Relationship, Drug; Ethylketocyclazocine; Female; Fentanyl; Methadone; Morphine; Naloxone; Phenazocine; Phencyclidine; Pyrrolidines; Time Factors

The effects of several opioid agonists and the opioid antagonist naloxone were examined in rats responding under a fixed-consecutive-number (FCN) schedule. Under this schedule, a reinforced response run consisted of responding eight or more times on one response lever, and then responding once on a second response lever. In one component of this schedule, an external discriminative stimulus signalled the completion of the response requirement on the first lever, whereas no stimulus change was programmed in the other. Morphine, l-methadone, U50488, ketocyclazocine, phencyclidine, and (+/-)N-allylnormetazocine decreased the percent of reinforced response runs (accuracy) under the FCN schedule without the external discriminative stimulus, but had no effect under the FCN schedule with the external discriminative stimulus. Naloxone and bremazocine, in contrast, had no effect on the accuracy of the discrimination under either FCN schedule. With the exception of bremazocine and U50488, which increased rates of responding at low doses, all drugs produced comparable decreases in rates of responding under both FCN schedules. During tests of antagonism, a 0.1 mg/kg dose of naloxone reversed completely the accuracy-decreasing effects produced by U50488 and morphine. The rate-decreasing effects of morphine and U50488 were reversed completely by a 0.01 and 1.0 mg/kg dose of naloxone, respectively. These results suggest that the addition of an external discriminative stimulus can modulate the disruptive effects of opioids, and that mu, sigma and some kappa agonists produce similar effects when evaluated under the FCN schedules.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Benzomorphans; Conditioning, Operant; Cyclazocine; Discrimination Learning; Ethylketocyclazocine; Male; Methadone; Morphine; Naloxone; Narcotics; Phenazocine; Pyrrolidines; Rats; Reinforcement Schedule

Tolerance to the behavioral effects of selected opiate compounds (cyclazocine, ketocyclazocine, naloxone and the stereoisomers of N-allylnormetazocine) and phencyclidine was evaluated using cumulative dosing procedures in rhesus monkeys responding under a fixed-ratio (FR) schedule of food presentation. Initially, the i.v. injection of graded doses of each drug in 8-min time-out periods preceding sequential FR periods decreased responding after each time-out in dose-related fashion. Subsequently, daily administration of up to 11 mg/kg of cyclazocine led to an approximately 16 to 32-fold rightward shift in the dose-effect curves for cyclazocine and ketocyclazocine and an approximately 4-fold rightward shift in the dose-effect curves for phencyclidine and (+)-N-allynormetazocine. In contrast, the dose-effect curves for naloxone and (-)-N-allynormetazocine were generally unchanged or shifted leftward. Termination of daily cyclazocine administration produced signs of withdrawal which disappeared over several days in all monkeys. These included emesis, frequent aggressive display and disruption of schedule-controlled performance. Present results suggest that the rate-decreasing effects of racemic cyclazocine involve mechanisms distinct from those mediating the rate-decreasing effects of naloxone or (-)-N-allynormetazocine. The differing degrees of cross-tolerance produced to the rate-decreasing effects of ketocyclazocine and of phencyclidine and (+)-N-allynormetazocine also suggest that the latter compounds produce behavioral effects to some extent through mechanisms distinct from those through which ketocyclazocine is effective.

Topics: Animals; Behavior, Animal; Cyclazocine; Dose-Response Relationship, Drug; Drug Tolerance; Ethylketocyclazocine; Food; Macaca mulatta; Male; Naloxone; Phenazocine; Phencyclidine; Stereoisomerism; Substance-Related Disorders

The study was designed to determine and compare the acute effects of the enantiomers of mu, kappa and sigma opioid agonists on the cortical EEG with the spectral analysis technique. The relative ability of naloxone to antagonize such effects was also assessed. Adult female Sprague-Dawley rats were implanted with chronic cortical EEG and temporalis muscle EMG recording electrodes, and with permanent indwelling external jugular cannulae. (-)-Methadone(mu agonist) produced increases in spectral power over the zero to 10Hz range, while (-)-ketocyclazocine (kappa agonist) produced increases in the 5-8 Hz band as a predominant peak. The(+) enantiomers of methadone and ketocyclazocine were inactive. The drug (+)-SK-10,047 (sigma agonist), produced a predominant spectral peak in the 7-9 HZ band that was associated with behavior that suggested psychotomimetic effects. The effects of morphine (mu agonist) on EEG and EEG power spectra were more sensitive to antagonism by naloxone than those produced by ketocyclazocine. The effects of (+/-)-SKF-10,047 and (+)-SKF-10,047 were not antagonized by 10 mg/kg of naloxone, while the effects of (-)-SKF-10,047 were partially antagonized by 10 mg/kg of naloxone. These findings further delineate the specificity of the differential effects of mu, kappa and sigma opioid agonists on the EEG and EEg power spectra in the rat.

Topics: Animals; Cerebral Cortex; Cyclazocine; Electroencephalography; Ethylketocyclazocine; Female; Methadone; Molecular Conformation; Morphine; Phenazocine; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu; Receptors, sigma

Opioid agonists were used to investigate the modulation of seizures mediated by mu, kappa and delta opiate receptors in the seizure-sensitive Mongolian gerbil. Morphine (1.0-25 mg/kg, s.c.) were used as prototypic agonists for mu, kappa and delta opiate receptors. Each opioid decreased the incidence and severity of the seizure as compared to control values. The anticonvulsant effects of morphine (10 mg/kg, s.c.) and ketocyclazocine (0.5 mg/kg, s.c.) were reversed by naloxone (1.0 mg/kg, s.c.), while the anticonvulsant effects of N-allylnormetazocine (2 mg/kg, s.c.) were not significantly changed by naloxone. Additionally, abnormal behavior was observed following administration of the opioids. Morphine (10 mg/kg, s.c.) produced excitation and hyperresponsiveness with intermittent cataleptic-like states. Ketocyclazocine (10 mg/kg, s.c.) predominantly produced a stuporous, immobile state, accompanied by some loss of posture. N-allylnormetazocine (10 mg/kg, s.c.) produced ataxia and stereotypic side-to-side head nodding . Naloxone was able to reverse the behavioral effects produced by morphine and ketocyclazocine but not those produced by N-allylnormetazocine. The data presented are consistent with earlier studies which demonstrated the anticonvulsant effects of beta-endorphin in the gerbil. This study further suggests that opioids have a protective role against seizure activity in the gerbil and the opioid anticonvulsant effect is not specific to one type of opioid agonist.

Topics: Animals; Anticonvulsants; Behavior, Animal; Cyclazocine; Electroencephalography; Ethylketocyclazocine; Female; Gerbillinae; Male; Morphine; Narcotics; Phenazocine; Receptors, Opioid; Receptors, Opioid, delta; Receptors, Opioid, kappa; Receptors, Opioid, mu; Seizures

The experiments reported here characterized the partial generalizations that prototype opiate drugs may produce in rats that are trained to discriminate 0.04 mg/kg of fentanyl from saline. Cyclazocine, nalorphine, ketocyclazocine and N-allylnormetazocine produced partial generalization with fentanyl; the same compounds also partially antagonized fentanyl. The fentanyl-like and the fentanyl-antagonist effects of these compounds occurred within similar ranges of dose. An orderly incompatibility was apparent between the agonist and antagonist effects produced by each drug; cyclazocine, for example, was unlikely to antagonize fentanyl in animals in which it produced generalization, whereas it did antagonize fentanyl in animals in which it produced no generalization. Cyclazocine, nalorphine, N-allylnormetazocine and naloxone produced either fentanyl-like or fentanyl-antagonist effects in all animals tested. A reliable relationship was apparent among the agonist and antagonist effects of different opiate drugs; rats that generalized cyclazocine also were likely to generalize nalorphine and ketocyclazocine and were relatively less responsive to cyclazocine, nalorphine, N-allylnormetazocine and naloxone as antagonists of fentanyl. The results point to the importance of a number of new methods in the analysis of drug discrimination data. Among these are the analysis of individual generalization data and the examination of agonist and antagonist effects of test drugs in the same animals. A parsimonious molecular interpretation of the data can be offered by assuming that morphine, ketocyclazocine, cyclazocine, nalorphine, N-allylnormetazocine and naloxone have affinity for, but differ in activity at, an opiate receptor where fentanyl acts to produce discriminative effects.

Topics: Animals; Conditioning, Operant; Cyclazocine; Discrimination Learning; Ethylketocyclazocine; Fentanyl; Male; Morphine; Nalorphine; Naloxone; Narcotics; Phenazocine; Rats; Rats, Inbred Strains; Sodium Chloride

The hypothesis that the nociceptive state and opiate-induced antinociception are generally regulated by Ca2+ brain levels has been tested. In this context, the effects of intracerebroventricular injections of CaCl2 (0.1-0.5 mumol), D600 (5.0-10.0 micrograms) and EGTA (0.5-1.0 mumol) on ethylketocyclazocine (EKC), ketocyclazocine (KC), Mr-2033, pentazocine (PTC), bremazocine (BMC) and SKF 10,047-induced antinociception were investigated in the mouse tail immersion test. Simultaneous treatment with either D600 or EGTA resulted in a significant and dose-related enhancement in the activities of the kappa-agonists: EKC, KC and Mr-2033, whilst the activities of PTC, BMC and SKF 10,047 remained unchanged. CaCl2 readily blocked the activities of all benzomorphans tested except that of SKF 10,047 against which CaCl2 was less effective. In addition a dose-related hyperalgesia was observed when CaCl2 was given alone. Although the results obtained from the kappa-agonists and CaCl2 per se support the hypothesis in question, data obtained from PTC, BMC and SKF 10,047 tends to oppose it. Additionally the present results taken together indirectly substantiate the notion that benzomorphan-induced analgesia may involve different opiate-sensitive neuronal substrates.

Topics: Analgesia; Analgesics; Analgesics, Opioid; Animals; Benzomorphans; Calcium; Calcium Channel Blockers; Cyclazocine; Egtazic Acid; Ethylketocyclazocine; Gallopamil; Male; Mice; Morphinans; Pentazocine; Phenazocine

Intracerebroventricular administration of all three prototype non-peptide opioid receptor (mu, kappa and sigma) agonists, morphine, ketocyclazocine and N-allyl-normetazocine (SKF 10,047) induced hyperthermia in rabbits. Similar administration of peptide opioids like beta-endorphin (BE), methionine-enkephalin (ME) and its synthetic analogue D-ala2-methionine-enkephalinamide (DAME) also caused hyperthermia. As expected, the synthetic enkephalin DAME was more potent than the parent enkephalin. Of the three anion transport systems (iodide, hippurate and liver-like or L) present in the choroid plexus, it is suggested that only the L transport system seems to be important to ventricular inactivation of BE and DAME since iodipamide (an inhibitor of the L transport system) augmented the hyperthermia produced by BE and DAME. Prostaglandins (PG) and norepinephrine (NE) were not involved in peptide and non-peptide opioid-induced hyperthermia because a PG synthesis inhibitor, indomethacin, and an alpha-adrenergic receptor blocker, phenoxybenzamine, had no thermolytic effect on them. Likewise cAMP was not required since a phosphodiesterase inhibitor, theophylline, did not accentuate the hyperthermia due to peptide and non-peptide opioids. Naloxone-sensitive receptors were involved in the induction of hyperthermia by morphine. BE, ME and DAME since naloxone attentuated them. In contrast, the hyperthermic response to ketocyclazocine and SKF 10,047 were not antagonized by naloxone.

Topics: Animals; beta-Endorphin; Body Temperature; Cyclazocine; Endorphins; Enkephalin, Methionine; Enkephalins; Ethylketocyclazocine; Male; Morphine; Naloxone; Peptides; Phenazocine; Rats

Topics: Animals; Cerebral Cortex; Cyclazocine; Electroencephalography; Ethylketocyclazocine; Female; Methadone; Phenazocine; Rats; Rats, Inbred Strains; Receptors, Opioid; Receptors, Opioid, kappa; Receptors, Opioid, mu; Receptors, sigma; Stereoisomerism

We have shown previously that acute morphine administration markedly enhances naloxone-induced increases in serum luteinizing hormone (LH) levels in the male rat. The purposes of the present studies were to determine whether this effect was opiate-specific and, if so, whether it was mediated by mu, kappa or sigma opiate receptors. In agreement with our previous reports, we found that naloxone-induced increases in serum LH levels were markedly enhanced (greater than 400%) in morphine-pretreated rats, relative to controls, 6 to 8 hr after a single injection; furthermore, similar effects were observed with all mu agonists assessed with the order of potency being etorphine greater than levorphanol greater than morphine greater than methadone greater than codeine. In contrast, we were unable to demonstrate any enhancement of the effects of naloxone on serum LH levels by ketocyclazocine, cyclazocine or SKF 10,047, prototypic ligands for kappa and sigma binding sites in brain. Finally, we observed that neither ethanol nor Nembutal induced a period of supersensitivity to the effects of naloxone on LH, even though both compounds transiently depressed serum LH levels over a time course similar to that observed for the opiates. On the basis of these results, it appears that the phenomenon of opiate-induced enhancement of the effects of naloxone on serum LH levels is opiate specific and, most importantly, is a unique feature of mu opiate agonists. The mechanisms underlying this phenomenon are unclear, but our results suggest that as yet unidentified events occurring within the hypothalamus must be responsible.

Topics: Animals; Binding, Competitive; Cyclazocine; Ethanol; Ethylketocyclazocine; Kinetics; Luteinizing Hormone; Male; Morphine; Naloxone; Pentobarbital; Phenazocine; Rats; Rats, Inbred Strains; Receptors, Opioid

Several distinct classes of opiate receptors have been postulated. It has been suggested that two of these, the kappa and sigma, may play a role in the initiation of feeding. The putative sigma receptor agonist N-allylnormetazocine increased food intake at doses of 0.1 and 1 mg/kg, whereas higher doses caused a decreased intake under some conditions. This stimulatory effect increased after repeated injections and was naloxone reversible. After repeated injections of N-allylnormetazocine, the feeding response to ketocyclazocine, but not morphine, appeared at an earlier point than in naive rats. These experiments support the suggestion that the sigma receptor may play some role in the initiation of feeding.

Topics: Animals; Cyclazocine; Dose-Response Relationship, Drug; Drug Interactions; Eating; Ethylketocyclazocine; Male; Morphine; Naloxone; Phenazocine; Rats; Rats, Inbred Strains; Receptors, Opioid

Rats were trained in a three-choice morphine (3.0 mg/kg), cyclazocine (0.3 mg/kg) and saline discrimination using a discrete-trials avoidance procedure. Behavior was considered to be under stimulus control when an animal reliably completed at least 18 trials of a 20-trial session on the correct lever after s.c. administration of either morphine, cyclazocine or saline. In tests of stimulus generalization, levorphanol produced a dose-related increase in trials completed on the morphine choice lever, whereas its optical enantiomer, dextrorphan, produced predominantly cyclazocine-appropriate responding, indicating that stimulus control of behavior was stereoselective. Ethylketocyclazocine, ketocyclazocine, levallorphan and SKF 10,047 engendered stimulus control of behavior that was unambiguously cyclazocine-like. In contrast, three other opioids with mixed agonist and antagonist properties occasioned responding on both the morphine- and cyclazocine-appropriate choice levers consistent with the mixture of morphine- and cyclazocine-like activity exhibited by these drugs in other procedures in animals and man. The stimulus effects of phencyclidine, a nonopioid compound, were not clearly interpretable within the present experimental context. This three-choice discrimination paradigm provides an approach for studying concurrently the morphine- and cyclazocine-like discriminative stimulus effects of opioids with multiple components of action and may lead to a more precise characterization of the stimulus properties of mixed-acting opioids than has been possible with conventional two-choice discrimination paradigms alone.

Topics: Animals; Cyclazocine; Discrimination Learning; Discrimination, Psychological; Ethylketocyclazocine; Male; Morphine; Narcotic Antagonists; Narcotics; Phenazocine; Phencyclidine; Rats; Sodium Chloride; Stereoisomerism

In each of two components of a multiple schedule, patas monkeys were required to respond on a right or left lever depending upon the stimulus combination (a color and a geometric form) presented. Reinforcement of a response in the presence of one stimulus (the form) was conditional upon the other stimulus (the color). The completion of a two-member chain of discriminations produced a food pellet. Errors produced a brief time-out. One component of the multiple schedule was a repeated-acquisition task where the discriminative stimuli for left- and right-lever responses changed each session (learning). In the other component, the discriminative stimuli were the same each session (performance). Morphine, ketocyclazocine and SKF 10,047 each produced dose-related decreases in overall rate of responding in both components of the multiple schedule. However, each drug affected the patterning of responding in a different manner. Across a range of doses which decreased response rate, neither morphine nor ketocyclazocine affected accuracy of the discriminations. In contrast, SKF 10,047 and its enantiomers produced a dose-dependent disruption of accuracy; errors were increased in the acquisition component at doses lower than those required to disrupt the discrimination in the performance component. The effects of the l-isomer of SKF 10,047 were generally comparable to those of the racemate. In comparison to the racemate, the d-isomer of SKF 10,047 was found to produce greater error-increasing effects in the acquisition component and smaller rate-decreasing effects in both components of the multiple schedule. In general, the effects of cyclazocine and pentazocine on both accuracy and rate of responding were comparable to those obtained with SKF 10,047. The results suggest that in patas monkeys, opioids with activity at the putative sigma receptor such as SKF 10,047, cyclazocine and pentazocine exert a dose-dependent disruptive effect on the accuracy of discriminations, an action not shared by prototypical mu and kappa opioid agonists, at doses which produce approximately equivalent rate-decreasing effects.

Topics: Animals; Behavior, Animal; Conditioning, Psychological; Cyclazocine; Discrimination Learning; Dose-Response Relationship, Drug; Erythrocebus patas; Ethylketocyclazocine; Male; Morphine; Pentazocine; Phenazocine; Psychomotor Performance

The effects of morphine, ketocyclazocine, cyclazocine, and SKF-10,047 were tested alone and in conjunction with naltrexone or naloxone, in rats responding under a multiple fixed-interval 3-min schedule of food presentation. Under this paradigm, electric shock was delivered on a fixed-ratio schedule for responses occurring during alternate schedule components. All of the drugs (except naltrexone and naloxone) decreased average rates of responding maintained by the unpunished component in a dose-dependent manner. The rate-decreasing effects of morphine and ketocyclazocine were antagonized by naltrexone. The rate-decreasing effects of cyclazocine were only slightly reversed by the antagonists, while those effects of SKF-10,047 were not affected by naltrexone. In some animals, certain doses of SKF-10,047 increased unpunished responding. This rate-increasing effect was antagonized by naltrexone. Morphine, ketocyclazocine, cyclazocine, and SKF-10,047 increased responding that was suppressed by electric shock, and these increases were antagonized by naltrexone and naloxone. Thus, the antagonism of opiate effects by narcotic antagonists depends in part on the behavior being evaluated.

Topics: Animals; Conditioning, Psychological; Cyclazocine; Dose-Response Relationship, Drug; Ethylketocyclazocine; Male; Morphine; Naloxone; Naltrexone; Narcotic Antagonists; Narcotics; Phenazocine; Punishment; Rats; Rats, Inbred Strains; Receptors, Opioid

Topics: Analgesics; Animals; Behavior, Animal; Clonidine; Cyclazocine; Ethylketocyclazocine; Male; Morphine; Motor Activity; Phenazocine; Rats; Receptors, Dopamine; Spiperone