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P H Warren

Publications and source records attributed to P H Warren.

10 recordsLinked to original sources
PubMed1989

Effects of kappa opioids on schedule-controlled behavior of squirrel monkeys.

The behavioral effects of U50,488 [( trans]-3,4-dichloro-N-methyl-N[2-(1- pyrrolidinyl)cyclohexyl]benzeneacetamide), bremazocine, Mr2266 [(-)-5,9-diethyl-2-(3-furylmethyl)-2'-hydroxy-6,7-benzomorphan] and morphine were compared in squirrel monkeys responding under multiple fixed-ratio fixed-interval (FR FI) schedules of food presentation or stimulus-shock termination. Doses of bremazocine (0.001-0.003 mg/kg), U50,488 (0.03-0.1 mg/kg) and Mr2266 (1.0-3.0 mg/kg) that markedly increased overall rates of FI responding maintained by stimulus-shock termination had little effect on or only decreased overall rates of FI responding maintained by food presentation. Each of the kappa opioids decreased FR responding maintained by either consequence. Morphine (0.03-1.7 mg/kg) only decreased responding under all conditions. Pretreatment with Mr2266 (0.1 mg/kg) produced a 10-fold or more rightward shift in the dose-effect functions for morphine under the two multiple schedules and U50,488 under the multiple schedule of food presentation. A 3-fold higher dose of Mr2266 produced an approximately 10-fold rightward shift in the descending portion of the dose-effect functions for U50,488 and bremazocine under the schedule of stimulus-shock termination but did not appreciably alter their rate-increasing effects. Naltrexone (0.1 mg/kg) antagonized the effects of selected doses of morphine or bremazocine on overall rates of responding under the schedule of stimulus-shock termination. In contrast to its effects in combination with morphine, however, naltrexone (0.1-3.0 mg/kg) did not block alterations in patterns of FI responding produced by bremazocine.(ABSTRACT TRUNCATED AT 250 WORDS)

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1989

Environmental determinants of enhanced sensitivity to the behavioral effects of naltrexone.

Dose-effect curves for naltrexone were determined in three squirrel monkeys studied sequentially under four different schedule conditions: a schedule of shock postponement; a fixed-interval schedule of shock presentation; a fixed-ratio schedule of food presentation; and a fixed-ratio schedule of stimulus-shock termination. In general, responding under the shock-postponement or the fixed-interval schedules was decreased minimally by doses of naltrexone up to 30 mg/kg, and these effects were not altered appreciably after daily injections of naltrexone under the fixed-interval schedule. Under the fixed-ratio schedule of food presentation naltrexone (0.3 to 10 mg/kg) produced dose-related decreases in responding, and after repeated daily injections of naltrexone the dose-effect curve was shifted more than 3-fold to the left. Under the fixed-ratio schedule of stimulus-shock termination, however, this supersensitivity to naltrexone was not apparent: responding was decreased appreciably only after 17.6 mg/kg of naltrexone. When the fixed-ratio schedule of food presentation was reinstated, the supersensitivity to naltrexone observed previously under this schedule was not evident initially, but reappeared quickly in two of the monkeys. The greater rate-decreasing effects of naltrexone under the fixed-ratio schedules compared to the other schedules may reflect a dependency related to the control rate of responding. Supersensitivity to naltrexone occurred only under the fixed-ratio schedule of food presentation and could be reversed temporarily by intervening exposure to the schedule of stimulus-shock termination. These results extend earlier findings that the behavioral effects of drugs can be dependent upon both past and present environmental influences.

Animals↗
PubMed1985

Impairment in auditory and visual function follows perinatal viral infection in the rat.

Acoustic startle reflexes are elicited by intense tone bursts but inhibited if weak bursts precede reflex elicitation. Rats were infected by intracerebral inoculation with lymphocytic choriomeningitis virus (LCMV) at birth. Compared to control animals, infected animals had higher elicitation and inhibition thresholds and showed recruitment at intense stimulus levels. Histopathology revealed both cochlear and retinal degeneration. Like some infectious agents in humans, perinatal exposure to LCMV in the rat yields a severe polysensory neuropathy.

Animals↗
PubMed1985

Effects of quaternary naltrexone and chlordiazepoxide in squirrel monkeys with enhanced sensitivity to the behavioral effects of naltrexone.

Dose-effect curves were determined for the effects of the opioid antagonist, naltrexone, on lever-pressing responses of squirrel monkeys maintained under a 30-response fixed-ratio schedule of food presentation. Cumulative doses of naltrexone up to 3 mg/kg i.m. had little or no effect on fixed-ratio responding, whereas higher doses reduced responding in all monkeys. After initial determinations of the dose-effect curve for naltrexone, repeated daily injections of high doses of naltrexone resulted in enhanced sensitivity to its behavioral effects. The cumulative dose-effect curve for naltrexone determined after termination of daily injections was shifted more than 3-fold to the left. In these same monkeys, the dose-effect curve for naltrexone methobromide, a quaternary derivative of naltrexone with limited access to the central nervous system, was similar to the initial dose-effect curve for naltrexone. Chlordiazepoxide given 1 hr before the experimental session shifted the naltrexone dose-effect curve back toward its initial position before the regimen of daily injections, but had no systematic effect on the dose-effect curve for quaternary naltrexone. Enhanced sensitivity to the behavioral effects of naltrexone in these experiments appears to depend on a central component of action and is attenuated by chlordiazepoxide.

Animals↗
PubMed1984

Stressors produce a concurrent decrease and increase in reflex amplitude in rats treated with naloxone.

The effect of inescapable foot-shock on the tail-flick response and on the startle response to brief shocks and brief tones was studied in rats. In the first experiment, 25 minutes of inescapable foot shock (stressor) produced a significant increase in tail-flick latency which was antagonized by the opioid antagonist naloxone (2.0 mg/kg). In the second experiment, the startle response to an electric shock to the tail was significantly diminished by the stressor, and this effect was not significantly reduced by naloxone. However, the size of the startle response to a brief tone was significantly increased in rats treated with naloxone. Thus, rats injected with naloxone had a decreased startle to shock but an increased startle to tone following inescapable foot shock. Finally, tones which preceded shocks by one second produced a facilitation of the startle response to the shocks in tests that followed exposure to the stressor. This facilitation was not affected significantly by naloxone. These results indicate that the changes in the startle response following the stressor were not mediated exclusively by endogenous opioids.

Acoustic Stimulation↗
PubMed1982

Selective action of morphine on reflex expression to nociceptive stimulation in the rat: a contribution to the assessment of analgesia.

In two experiments startle reflexes to both loud noises and electric shocks were elicited in rats. The two stimuli were paired so that the inhibitory effect of each stimulus on the response to the other could be assessed. In the first study it was shown that morphine (0-16 mg/kg) had a selective and dose related depressive effect on the response to shock. The response to a leading tone and inhibition produced by the shock on the response to a following tone were minimally affected. In the second study, morphine (10 mg/kg) again depressed the reaction to shock but not to tone, and its effect was antagonized by naloxone (10 mg/kg). The selective effect on responses to shock, leaving responses to tone relatively unaffected, reveals that reflex depression should not be attributed to a loss in motor functions. Further, that morphine had little effect on reflex inhibition produced by the shock suggests that the nociceptive properties of shock were affected rather than simple sensory processes. It is proposed that the method described here is useful for assessing changes in nociception in laboratory animals, and for discriminating between nociceptive, afferent, and efferent processes.

Acoustic Stimulation↗
PubMed1980

Attenuated aversiveness of electric shock during nitrous oxide exposure.

The analgesic properties of nitrous oxide (N2O) were evaluated with a fractional escape procedure ("shock titration" schedule). Shock intensity rose by a small step every few seconds. Each designated response by a rat or squirrel monkey subject reduced the amplitude of the shock by one step. Both species maintained stable tolerated levels of shock when exposed to pure oxygen or to air. Exposure to N2O yielded an elevation in maintained shock level whose magnitude depended on concentration. Statistically significant rises generally were apparent at N2O concentrations of 30 to 70%, which also tended to reduce shock level fluctuations. Since the raised shock levels were not accompanied by changes in overall response rate, they can be attributed to the analgesic properties of N2O.

Analgesics↗
PubMedDate not supplied

Hyperreflexive behavior in Brattleboro rats.

In two experiments we compared the size of the startle response elicited by shock and acoustic stimuli in animals having a congenital absence of vasopressin (Brattleboro rats) with closely related controls, which do synthesize vasopressin. The rats lacking vasopressin were hyperresponsive to both shock and acoustic stimuli. Inhibition of the acoustic startle by shock prestimuli also was greater in these animals. These results are consistent with reports which indicate that vasopressin attenuates responses to noxious stimuli.

Acoustic Stimulation↗