ici-154129 and Pain

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Arthritis; Arthritis, Experimental; Benzomorphans; beta-Endorphin; Dynorphins; Endorphins; Enkephalin, Leucine; Enkephalin, Methionine; Morphine; Naloxone; Nociceptors; Pain; Pituitary Gland, Anterior; Protein Precursors; Pyrrolidines; Rats; Receptors, Opioid; Sensory Thresholds; Spinal Cord; Thalamus

This study examined the effects of chronic (7 day) administrations of opioid agonists, via osmotic minipumps (20 micrograms/microliters/h, or 2 mg/kg/h for each agent) on: 1) nociception and activity, and 2) the analgesic and locomotor responses of subordinate male mice experiencing social conflict (aggression without defeat) and defeat in a "resident-intruder" paradigm. Chronic infusion of the mu opioid antagonist, naltrexone, resulted in a hypoanalgesic response and a decrease in basal locomotor activity on days 3-7 postimplantation which returned to the basal levels of saline-implanted control mice after termination of the infusions on day 9. Naltrexone reduced defeat-induced analgesia on the second day after implantation, but had no consistent effects on analgesia on test days 6 and 9 or on the aggression-induced (nondefeat) analgesia and increases in activity. The delta opioid antagonist ICI-154, 129, while having no significant effects on basal nociception or locomotor activity, augmented nondefeat-induced analgesia (day 2) and reduced the defeat-induced increases in activity (days 2 and 6). The mu agonist, levorphanol, resulted in a significant analgesia on the first two days after infusion, followed by the development of tolerance to the analgesic effects over days 3-7. On day 9, a hypoanalgesic response indicative of withdrawal was evident. Levorphanol also induced a marked decrease in locomotor activity over days 3-7 postimplantation, with no evidence of the development of tolerance or withdrawal following termination of infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Animals; Conflict, Psychological; Enkephalin, Leucine; Infusion Pumps, Implantable; Levorphanol; Male; Mice; Motor Activity; Naltrexone; Narcotic Antagonists; Narcotics; Pain; Pyrrolidines; Receptors, Opioid; Social Behavior; Sodium Chloride

Exposure to either cold or warm stress increased the thermal nociceptive thresholds of the terrestrial snail, Cepaea nemoralis. The warm stress-induced 'analgesia' was blocked by the prototypic opiate antagonist, naloxone, and the delta-opiate antagonist, ICI 154,129, and was suppressed by a 24-h pretreatment with the irreversible opiate antagonist, beta-funaltrexamine (B-FNA). In contrast, cold stress-induced analgesia was unaffected by either naloxone, ICI 154,129 or B-FNA. These results indicate that this mollusc displays both opioid and non-opioid forms of stress-induced analgesia in a manner analogous to that reported for mammals. These findings suggest an early evolutionary development and phylogenetic continuity of opioid and non-opioid mediated stress responses to aversive environmental stimuli.

Topics: Animals; Cold Temperature; Endorphins; Enkephalin, Leucine; Hot Temperature; Naloxone; Naltrexone; Pain; Reaction Time; Snails; Stress, Physiological

We examined the effects of mu and kappa opiate agonists on the day- and night-time nociceptive, locomotory and ingestive behaviors of an island population of wild male and female deer mice, Peromyscus maniculatus triangularis. The prototypical mu opiate agonist, morphine, had significant analgesic and locomotory effects, which were blocked by naloxone, and the specific delta opiate antagonist, ICI 154,129, respectively. The specific kappa opiate agonist, U-50,488, had significant analgesic actions and inhibitory effects on locomotor activity, as well as stimulating feeding. Significant day-night variations occurred in the analgesic and activity responses, with the mu and kappa opiate agonists having significantly greater effects at night. There were also prominent sex differences in responses; male deer mice displaying significantly greater levels of mu and kappa opiate-induced analgesia and alterations in activity than female animals. These sex differences in opiate-induced effects were most pronounced at night, female deer mice displaying reduced day-night rhythms of responsiveness. These results demonstrate the existence of significant day-night rhythms and sex differences in the mu and kappa opiate behavioral responses of a wild population of rodents.

Topics: 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; Analgesics; Animals; Behavior, Animal; Circadian Rhythm; Enkephalin, Leucine; Feeding Behavior; Female; Male; Morphine; Motor Activity; Naloxone; Narcotic Antagonists; Narcotics; Pain; Peromyscus; Pyrrolidines; Sex Characteristics

The behavioural disturbances produced by acute exposure to ethanol have been related to changes in function of the opioid systems in the CNS. However, evidence in the literature is conflicting. The present report concerns the possible role of the enkephalinergic system in the mediation of acute ethanol effects. We used rats to study the ability of a selective opioid delta receptor antagonist (ICI 154129) to prevent the effect of ethanol on pain sensitivity, body temperature, sensorimotor performance and level of consciousness. Furthermore, in vitro receptor binding was measured to investigate whether or not ethanol, within a non-lethal concentration range, would change the binding parameters of the delta receptor ligand [3H][D-ala2, D-Leu5]enkephalin. ICI 154129 did not significantly influence the effects of ethanol in the behavioural experiments. Ethanol did not significantly change the binding parameters whether saturation or competition was measured in the receptor binding experiments. Thus, there was no evidence that the enkephalinergic system mediated the acute ethanol effects.

Topics: Animals; Behavior, Animal; Body Temperature; Enkephalin, Leucine; Enkephalin, Leucine-2-Alanine; Enkephalins; Ethanol; In Vitro Techniques; Narcotic Antagonists; Pain; Psychomotor Performance; Rats; Rats, Inbred Strains; Reaction Time; Receptors, Opioid

Antinociception produced in mice by a 3 min swim was attenuated by ICI 174,864 and by low doses of naloxone indicating the involvement of both delta- and mu-receptors. The degree of antinociception was not related to plasma corticosterone (CS) levels measured 11 min after the swim. Naloxone affected CS levels in control mice and appeared to reduce the CS response to stress: ICI 154,129 and ICI 174,864 did not produce consistent effects on plasma CS levels.

Topics: Analgesia; Animals; Enkephalin, Leucine; Hydrocortisone; Hypothalamo-Hypophyseal System; Male; Mice; Naloxone; Narcotic Antagonists; Pain; Pituitary-Adrenal System; Stress, Physiological

The selective opioid delta-receptor antagonist, ICI 154,129, attenuated the antinociception, assessed by prolongation of reaction time on the hot-plate, of mice which had swum for 3 min at 20 degrees C. This stress-induced antinociception was also sensitive to naloxone suggesting the involvement of both delta- and mu-receptors. A swim of 0.5 min at 30 degrees C did not produce antinociception on the hot plate but the writhing response to i.p. acetic acid was blocked by a non-opioid mechanism.

Topics: Animals; Enkephalin, Leucine; Escape Reaction; Male; Mice; Naloxone; Pain; Reaction Time; Receptors, Opioid; Receptors, Opioid, delta; Stress, Physiological; Swimming