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T S Shippenberg

Publications and source records attributed to T S Shippenberg.

81 records · Page 5Linked to original sources
PubMed1988

Motivational effects of opioids in an animal model of prolonged inflammatory pain: alteration in the effects of kappa- but not of mu-receptor agonists.

An unbiased preference conditioning procedure was used to characterize and compare the motivational effects of opioids in naive rats and those suffering from the prolonged pain associated with Freund's adjuvant (FA)-induced inflammation of one hind limb. The mu-opioid agonist morphine functioned as a reinforcer in naive animals, producing marked preferences for the drug-paired place. Similarly, rats injected with FA 7 days prior to conditioning exhibited a preference for the morphine place, and the magnitude of this effect did not differ between groups. Administration of the kappa-opioid receptor agonist U-69593 to naive rats produced dose-related place aversions. The aversive effect of this kappa-agonist was, however, abolished in FA-treated rats. Thus, regardless of the dose administered, U-69593 produced conditioning similar to that observed in response to saline. These data suggest that kappa-agonists may lack aversive effects in subjects experiencing prolonged noxious stimulation, and as such may be effective therapeutic agents in the management of chronic pain states.

Animals↗
PubMed1988

Tolerance and cross-tolerance to the discriminative stimulus properties of fentanyl and morphine.

The investigation tested the hypothesis that tolerance would develop to the discriminative stimulus properties of fentanyl upon discontinuation of discrimination training and injection of fentanyl in doses larger than the training dose. Rats were trained to discriminate an injection of fentanyl, 0.04 mg/kg, from saline using a two-lever choice procedure with food as a reinforcer. Given acutely, morphine substituted for fentanyl and was 100-times less potent. Subsequently, training was stopped, and fentanyl, 0.08 mg/kg, was injected every 12 hr for 1 week. This procedure did not produce tolerance nor did tolerance occur when fentanyl, 0.16 mg/kg every 24 hr, was continued for an additional week. In contrast, a dose of morphine (8.0 mg/kg) that was equated for efficacy to the 0.08-mg/kg dose of fentanyl produced both tolerance to the morphine stimulus and cross-tolerance to the fentanyl stimulus after 3 to 4 days of administration. In an additional experiment, the time course for detection of fentanyl was found to be significantly shorter than the time course for the detection of morphine. These results suggest that the present, as well as a previous, report of failure to find tolerance to the stimulus properties of fentanyl is perhaps attributable to fentanyl's brief duration of action. To test this hypothesis, 16 rats were trained to discriminate fentanyl, 0.04 mg/kg, and dose-effect data were obtained for the generalization of fentanyl and the substitution of morphine for this discriminative stimulus. Subsequently, training was stopped and fentanyl was injected for 4 days in a design that called for injection of 0.12 mg/kg every 6 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1987

Motivational properties of opioids: evidence that an activation of delta-receptors mediates reinforcement processes.

The role of central delta-opioid receptors in the mediation of opioid reinforcement and endogenous reward processes was examined using a non-biased place-preference conditioning procedure. Intracerebroventricular (i.c.v.) administration of the selective delta-receptor agonist, [D-Pen2, D-Pen5]-enkephalin (DPDPE, 10.0-25.0 micrograms) produced a significant preference for the drug-associated place and a similar effect was observed following i.c.v. injections of morphine (10.0 micrograms). Administration of the delta-receptor antagonist, ICI 174,864, at doses (1.0-5.0 micrograms, i.c.v.) which had no aversive effects when tested alone, abolished the reinforcing properties of DPDPE. Such treatment did not, however, modify the effect of morphine. These findings demonstrate the involvement delta- as well as mu-receptors in the motivational properties of opioids and suggest that the activation of either receptor type is sufficient for the elicitation of appetitively reinforcing effects.

Animals↗
PubMed1987

Place preference conditioning reveals the involvement of D1-dopamine receptors in the motivational properties of mu- and kappa-opioid agonists.

The role of D1 dopamine receptors in mediating the motivational properties of opioid agonists was investigated by use of place preference conditioning. Administration of the D1 receptor antagonist SCH 23390 (0.001-0.5 mg/kg) or the kappa-opioid receptor agonist U-69593 (0.16 mg/kg) produced conditioned place aversions. In contrast, the mu-opioid agonist, morphine (3.0 mg/kg) was appetitively reinforcing. Chronic infusion of SCH 23390 (1.0 mg/kg/day) during conditioning abolished the effects of both opioid agonists. These data demonstrate the specific involvement of D1 receptors in the motivational properties of mu- and kappa-opioid agonists and suggest that dopaminergic systems are crucial for the expression of both reinforcing and aversive motivational states.

Analgesics↗
PubMed1986

Differential effects of mu and kappa opioid systems on motivational processes.

The role of multiple opioid receptor types in mediating the motivational properties of opioid agonists and antagonists was investigated by means of a place-preference conditioning procedure. Mu-agonists produced positive reinforcing effects in drug-naive animals whereas kappa agonists and the opioid antagonist, naloxone, were aversive. Chronic infusion of naloxone during conditioning, at a dose sufficient to block mu- but not kappa-receptors, antagonized the effects of both morphine and naloxone. This treatment did not alter the aversion produced by the kappa agonist, U69593. These data demonstrate that opioid reinforcement results from an activation of mu-receptors whereas aversive effects are produced by either an antagonist action at this receptor or an activation of kappa receptors. Such results indicate that mu and kappa opioid systems differentially modulate motivational processes.

Analgesics↗
PubMed1981

A subhuman primate model for fetal alcohol syndrome research.

The object of this project was to develop and evaluate new methods for the establishment of a subhuman primate model (SPM) of the fetal alcohol syndrome (FAS). Adult Rhesus monkeys (5.5--16.0 kg) were used as subjects. All were proven breeders and all matings in this project were repeats of matings that had previously produced normal offspring. The animals received alcohol (ALC) via permanently implanted intragastric cannulae (IGC) at doses to establish blood alcohol concentrations (BAC) within 2 selected ranges. Initially the high dose group received ALC doses designed to maintain BAC of approximately 150 mg/100 ml, and the other at 75--100 mg/100 ml. Daily ad lib food intake was monitored. The animals received infusions of liquid diet through the IGC so that their daily intake of balanced calories was 110% of the minimum daily requirements. The overall experimental design of this study called for each animal to have on ALC exposed pregnancy, serve as a pair-fed control for its own ALC exposed pregnancy and serve as a pair-fed control for a different animal. The preliminary results indicate that the IGC was suitable for use in pregnant rhesus monkeys. Two animals that were receiving ALC at doses and schedules to maintain the BAC above 150 mg/100 ml aborted during the first trimester of their pregnancies. No abortions have been observed in animals receiving either control diets or lower doses of ALC. In summary, this preliminary study demonstrates that it is feasible to use an IGC as a method for maintaining precise control over a pregnant Rhesus monkey's ALC exposure and nutritional status and thereby establish a SPM of FAS that meets critical control criteria.

Animals↗
PubMedDate not supplied

A drug discrimination analysis of ethanol-induced behavioral excitation and sedation: the role of endogenous opiate pathways.

The drug discrimination technique was used to characterize the biphasic behavioral effects of ethanol (ETOH) and examine the role of opiate pathways in mediating ETOH's excitatory (EX) and sedative (SED) phase effects. Forty Sprague-Dawley rats were trained to perform ETOH vs. saline discriminations during either ETOH's EX (6 min post-dose) or SED (30 min post-dose) phase of action in a double-lever food reinforced operant paradigm. After animals had achieved the required performance criterion, dose-response and phase-generalization tests were conducted in each group. In addition, preliminary studies were conducted to examine the effect of naloxone (NLX) pretreatment on discrimination of ETOH's EX and SED phase stimulus effects. Results of generalization testing demonstrate that discrimination of ETOH was dose-dependent and there was no generalization between phases regardless of the initial training condition. NLX pretreatment significantly attenuated discrimination of ETOH's EX phase effects but was ineffective in antagonizing ETOH's SED effects. These data demonstrate that the stimulus properties of ETOH are phase-dependent and suggest that opiate pathways are critical for the expression of ETOH's EX phase behavioral effects.

Animals↗