naloxone and Catatonia

Topics: Animals; Behavior, Animal; Catatonia; Clinical Trials as Topic; Double-Blind Method; Endorphins; Enkephalins; Humans; Male; Naloxone; Rats; Schizophrenia; Vocalization, Animal

The effects of ketamine and morphine on pain perception and catalepsy were compared in rats. Analgesia, as measured by the latency to withdrawal of the tail from a 55 degrees C water bath (tail-flick latency difference, TFLD), was produced by both ketamine and morphine, but at widely different doses, and in each case the effect was reversed by naloxone. Catalepsy, measured by the duration of loss of righting reflex (DLRR) in catatonic animals, was induced by larger doses of both ketamine and morphine and in each case was reduced by a larger dose of naloxone. DLRR and TFLD tolerance developed rapidly and with a similar time course after daily doses of ketamine or morphine. Rats tolerant to the DLRR effect of ketamine showed cross-tolerance to morphine. Rats tolerant to the DLRR effect of morphine did not show cross-tolerance to ketamine when administered the following day; instead, these rats showed potentiation of the ketamine-induced DLRR. The degree of potentiation noted 24 hr after a single or multiple daily doses of 45 mg/kg of morphine is the same as that seen when 2 mg/kg of morphine is given simultaneously with ketamine. The residual brain level of morphine 24 hr after 45 mg/kg is similar to the level 1 hr after a 2-mg/kg dose. The augmented ketamine response in morphine-tolerant rats is postulated to be a result of residual morphine still present in the brain 24 hr after the last DLRR-inducing dose of morphine.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Analgesia; Animals; Catalepsy; Catatonia; Dose-Response Relationship, Drug; Drug Synergism; Drug Tolerance; Female; Ketamine; Morphine; Naloxone; Rats; Rats, Inbred Strains

Alfentanil, a short-acting and powerful analgesic, when injected peripherally to rats (0.5 mg/kg) produced a catatonic state characterized by a rigid akinesia. The present study was designed to explore the neuroanatomical location of the opiate receptors mediating the alfentanil induced catatonia. The catatonic effect of alfentanil was measured using a bar test and depression of locomotor activity in rats tested in photocell cages during an active nocturnal phase of their cycle. Methylnaloxonium HCl (MN), a quaternary derivative of naloxone which does not readily cross the blood-brain barrier, injected into the lateral ventricle significantly reduced the catatonia at doses of 0.125-2.0 micrograms as measured in both the locomotor and bar test. MN perfusion of similar doses directly into the nucleus raphe pontis, but not in the caudate nucleus significantly antagonized the catatonia. These data complement results on alfentanil-induced muscular rigidity (Blasco et al., see companion paper) where EMG indices of rigidity in rats were reversed by microinjections of low doses of MN (0.125 and 0.5 microgram) in the nucleus raphe pontis, but not the caudate nucleus even at a high dose (4.0 micrograms). Together these results suggest that the region of the nucleus raphe pontis is an important neural substrate for opiate-induced muscular rigidity, and that the catatonic state produced by opiates depends on more diffuse opiate receptor activation of which one important component may be the nucleus raphe pontis.

Topics: Alfentanil; Animals; Brain; Catatonia; Fentanyl; Male; Motor Activity; Naloxone; Quaternary Ammonium Compounds; Rats; Rats, Inbred Strains; Receptors, Opioid

Attempts to eliminate or reduce the rigidity induced with high-dose narcotic anesthesia in the operating room have been only partially successful. Previous investigations of opioid receptor sites mediating this rigidity have implicated two central regions: the nucleus raphe pontis (NRP) within the reticular formation and the caudate nucleus (CN) within the basal ganglia. The present study used systemically administered alfentanil (ALF), a potent, short-acting fentanyl analog, and intracerebrally infused methylnaloxonium (MN), a quaternary derivative of naloxone, to elucidate further the functional role of the NRP and CN in rigidity. ALF (0.5 mg/kg s.c.) produced a reliable model of rigidity, as documented by gastrocnemius electromyography. The onset of this rigidity was within 60 s of ALF administration, with a total duration of approximately 40-50 min. Intracerebroventricular (i.c.v.) injections of 2.0 or 4.0 micrograms of MN 15 min prior to ALF treatment prevented rigidity, while 0.125 or 0.5 microgram had no significant effect on rigidity. MN injected directly into the NRP at doses as low as 0.125 microgram significantly antagonized ALF-induced rigidity, while injections of MN into the caudate nucleus at doses as high as 4.0 micrograms failed to antagonize ALF-induced rigidity. These observations demonstrate that injection of MN into the NRP is at least 16-fold more effective in blocking ALF-induced rigidity than MN injected into the ventricle and, more importantly, at least 32-fold more effective than MN injected into the CN. The results suggest that the NRP may be an important site for the neural control of muscular rigidity associated with high-dose narcotic administration.

Topics: Alfentanil; Animals; Catatonia; Caudate Nucleus; Electromyography; Fentanyl; Male; Muscle Rigidity; Naloxone; Pons; Quaternary Ammonium Compounds; Raphe Nuclei; Rats; Rats, Inbred Strains

Some in vivo agonist and antagonist properties of the putative k-compound bremazocine were characterized in rats. Bremazocine, at doses from 0.015-32 mg/kg i.p., delayed nociceptive reaction on a 55 degrees C hot-plate with a dose-response curve not readily fitting a single straight line; this effect was antagonized by high doses of naloxone. In the same rats bremazocine did not delay the intestinal transit of a charcoal meal fed 5 min earlier and prevented morphine-induced constipation. This antagonism appeared to be opioid-specific and competitive, with apparent pA2 value 8.56. Catatonia induced by etorphine (0.004 mg/kg s.c.) and constipation induced by etorphine (0.004 mg/kg s.c.) and D-Ala2-D-Leu5-enkephalin (0.1 mg/kg i.p.) were completely antagonized by bremazocine (0.03-8 mg/kg i.p.). Antinociception induced by morphine (10 mg/kg i.v.) and etorphine (0.004 mg/kg s.c.) was only partly prevented. Naloxone (1 mg/kg) and bremazocine (0.015-1 mg/kg i.p.) precipitated a withdrawal syndrome, evaluated as jumping frequency, in rats rendered dependent to morphine. These data suggest the involvement of more than one opioid receptor population in bremazocine action in vivo.

Topics: Analgesics; Animals; Benzomorphans; Catatonia; Constipation; Dose-Response Relationship, Drug; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Etorphine; Gastrointestinal Motility; Humans; Male; Morphinans; Morphine; Naloxone; Rats; Substance Withdrawal Syndrome; Substance-Related Disorders

The intracerebroventricular injections in mice of the mu receptor agonists morphine and fentanyl induced an immobility state (the animals staying motionless with the head down on a 45 degree inclined plane) which was apparently hypertonic (catatonia ?) or at least enabled them to remain hanging on a horizontal wire with their forepaws. In similar conditions, injections of the kappa receptor agonists ketocyclazocine and bremazocine induced an immobility state which was hypotonic, in contrast with the preceding one. In a similar way to the mu agonists, Met-enkephalin or Leu-enkephalin injected i.c.v. in association with the inhibitor of enkephalinase thiorphan induced an apparently hypertonic immobility which was easily antagonized by naloxone. The association of thiorphan with bestatin (an inhibitor of aminopeptidases involved in enkephalins inactivation) produced similar results. In contrast, the hypotonic immobility induced by the kappa receptor agonists required relatively high doses of naloxone to be antagonized. The opiate antagonist MR 2266 antagonized equipotent doses of all the above mentioned agents with a similar efficacy. From these data it is suggested that enkephalins could induce an apparently tonic immobility by stimulating mu receptors and that endogenous enkephalins could be involved in a tonic mediation modulating the locomotor activity or regulating the muscular tone.

Topics: Animals; Benzomorphans; Catatonia; Cyclazocine; Enkephalins; Ethylketocyclazocine; Fentanyl; Humans; Immobilization; Injections, Intraventricular; Male; Mice; Morphine; Naloxone; Narcotic Antagonists; Narcotics

Topics: Animals; Catatonia; Humans; Male; Medulla Oblongata; Morphine; Movement Disorders; Naloxone; Pain; Rats; Rats, Inbred Strains

In June, 36 lizards (males and females) were injected with 0.01, 0.1, 1.0, 10.0, or 100 mg/kg of MIF-I, or the diluent vehicle, and placed in a cage for ten minutes. Tonic immobility (TI) was then induced on an open lab table. All doses of MIF-I significantly reduced TI duration as compared to the duration with the diluent alone. In subsequent experiments lizards were injected with 0.1 mg/kg of MIF-I, 0.1 mg/kg of naloxone, or the diluent vehicle, and placed in small aquaria for ten minutes. TI was then induced in the small aquaria. In July, using 60 females, MIF-I and naloxone slightly reduced the duration of TI, but not significantly, and overall TI durations were reduced as compared with the first experiment possibly because the lizards could escape from the view of the experimenter in the corners of the aquaria. A third experiment was done in late September and early October with 120 males and 120 females. No drug effect was seen, but there was a significant difference between the TI durations of males and females, the females having longer durations. A relationship between the difference in response to MIF-I and the breeding seasons of the lizards could not be determined due to the possibility that the change in experimental design after the June experiments may alone have accounted for the loss of the significant response to MIF-I.

Topics: Animals; Catatonia; Humans; Lizards; MSH Release-Inhibiting Hormone; Naloxone; Sex Factors; Time Factors

Topics: Animals; Apomorphine; Behavior, Animal; Catalepsy; Catatonia; Electric Stimulation; Female; Haloperidol; Humans; Naloxone; Rats; Seizures

Opiate receptor involvement in tonic immobility was examined by administering various does of the opiate antagonist naloxone before measuring morphine-potentiated, shock-poteniated or unpotentiated tonic immobility in chickens. Naloxone attenuated morphine-potentiated, but not shock-potentiated or unpotentiated tonic immobility. Morphine-potentiated tonic immobility appears to be opiate specific.

Topics: Animals; Catatonia; Chickens; Drug Interactions; Electroshock; Humans; Male; Morphine; Naloxone

The narcotic antagonist, naloxone, was microinjected into the head of the caudate nucleus (HC), periaqueductal gray matter (PG), and cerebellar white matter (CB) of rats to counteract the catatonia induced by systemic morphine. Naloxone produced a loss of the catatonic response when administered into HC or PG, but not when microinjected into CB. Isotonic saline in HC, PG, and CB did not counteract the catatonic effects of morphine. The reversal of catatonia was similar for naloxone injections in HC and PG. Both these areas have high concentrations of opiate receptors while CB has few opiate receptors. It is suggested that the HC and PG are involved in the reversal of the catatonic effects of morphine via the high concentrations of opiate receptors found there.

Topics: Animals; Catatonia; Caudate Nucleus; Cerebellum; Cerebral Aqueduct; Humans; Injections; Male; Morphine; Naloxone; Rats

Topics: Adult; Amobarbital; Catatonia; Humans; Injections, Intravenous; Male; Naloxone

Intraventricular administration of a peptide from ovine pituitaries whose structure is identical to the 61-91 C-terminal portion of beta-lipotropic hormone (61-91 beta-LPH) induced catalepsy, muscular hypertonus and analgesia in rats. Naloxone inhibited both the analgesic and cataleptic effects. 1-dihydroxyphenylalanine (1-DOPA) completely prevented the cataleptic effect. The cataleptic effect of 61-91 beta-LPH was potentiated by 1-5-hydroxytryptophan (5-HTP).

Topics: 5-Hydroxytryptophan; Animals; beta-Lipotropin; Catalepsy; Catatonia; Dose-Response Relationship, Drug; Humans; Levodopa; Naloxone; Rats; Sheep; Tremor

The endogenous morphinomimetic brain peptides Met5-enkephalin and alpha-, beta-, and gamma-endorphins have been evaluated in rats after intracerebrospinal fluid injection. beta-Endorphin produces marked, prolonged muscular rigidity and immobility similar to a catatonic state, counteracted by the opiate antagonist naloxone; this effect occurs at molar doses 1/100 to 1/400 that at which the other peptides or morphine block the response to painful stimuli. All peptides evoked dose-related, naloxone-reversible, wet-dog shakes in rats that had not been exposed to drugs. beta-Endorphin produced hypothermia, whereas gamma-endorphin produced hyperthermia. Such potent and divergent responses to naturally occurring subtances suggest that alterations in their homeostatic regulation could have etiological significance in mental illness.

Topics: Animals; Behavior, Animal; Body Temperature; Catatonia; Dose-Response Relationship, Drug; Humans; Naloxone; Nerve Tissue Proteins; Oligopeptides; Peptides; Receptors, Opioid; Reflex; Structure-Activity Relationship

Topics: Animals; Behavior, Animal; Blepharoptosis; Brain; Catalepsy; Catatonia; Electric Stimulation; Electrodes, Implanted; Exophthalmos; Haloperidol; Humans; Hypothalamus; Male; Morphine; Naloxone; Rats; Self Stimulation