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Biomedical subjects

C X Poulos

Publications and source records attributed to C X Poulos.

At least 37 records · Page 2Linked to original sources
PubMed1989

Naloxone-induced analgesia: effects of the benzodiazepine antagonist Ro 15-1788.

Repeated exposure to pain under the influence of the opiate antagonists naloxone and naltrexone leads to the recruitment of substantial analgesia as measured by paw-lick latency on the hot-plate test (4,11). One hypothesis to explain this naloxone-induced analgesia (NIA) is that nociceptive stimulation in the face of opiate blockade becomes stressful enough to activate an analgesic adaptation that otherwise would not occur. This hypothesis was examined in two experiments by the administration of a benzodiazepine antagonist with anxiogenic properties (Ro 15-1788, in a dose of 10 mg/kg) in conjunction with repeated administrations of naloxone (5 mg/kg). One experiment incorporated defecation as a relatively direct measure of stress. Ro 15-1788 reliably augmented NIA. Defecation was increased by naloxone alone and in combination with Ro 15-1788. Overall, the results were most consistent with the hypothesis that NIA is a form of stress-induced analgesia that is at least partly nonopiate in nature.

Analgesia↗
PubMed1989

"Cravings" are ambiguous: ask about urges or desires.

Despite the dictionary definition of "craving" (a strong desire), two studies indicate that a substantial percentage of persons with alcohol and drug problems use the word "craving" to mean any desire or urge, even a weak one, to use substances. Researchers and clinicians are advised to beware of this ambiguity of "craving" and to consider the conceptual status of "craving" in their work.

Adult↗
PubMed1988

Tolerance to morphine analgesia is reduced by the novel addition or omission of an alcohol cue.

A recent study demonstrated that ethanol tolerance was reduced by the presentation of a novel extraneous stimulus at the time of test. In Pavlovian terms, this phenomenon is known as external inhibition. The present study sought to determine whether a drug cue could act as an external inhibitor of tolerance. Theoretically, either the occurrence of an unexpected stimulus or the nonoccurrence of an expected one can operate to disrupt already established conditioned responses. This prediction was assessed in the present study by the novel presentation or the novel omission of a drug cue at test. Two groups of rats were made completely tolerant to the analgesic effects of morphine. During tolerance acquisition the groups were treated identically except that one group always received a dose of alcohol 15 min following morphine. At test, animals experienced either the novel introduction or the novel omission of the alcohol cue. Both manipulations led to a reduction of morphine analgesia. Beyond their theoretical importance, these results have clinical implications in view of the frequency of multiple concurrent drug abuse.

Analgesia↗
PubMed1988

"Paradoxical" analgesia induced by naloxone and naltrexone.

Analgesic effects of pellet implantation of the opiate antagonists naloxone and naltrexone and of chronic administration of naloxone by subcutaneous injection were examined. Rats were implanted with a slow-release pellet containing 10 mg naloxone or 10 mg naltrexone and tested for paw-lick latency on a hotplate apparatus. Controls were implanted with placebo pellets or given saline injections as appropriate. There were five test trials at intervals up to 72 h after implantation of naloxone and up to 120 h after the implantation of naltrexone. In a separate experiment, 5 mg/kg naloxone was injected; there were single trials on 5 consecutive days. All drug-treated animals displayed clear and substantial analgesia by their second test trial. This "paradoxical" analgesia was gradually reversed in the pellet-implant groups as tissue levels of the antagonists declined, but increased progressively with each trial involving injections. It was hypothesized that blockade of endogenous opiates by antagonists resulted in a form of "super-pain" on the hotplate, which in turn activated a normally redundant "backup" analgesic system. The results with naloxone injections show that unlike opiate-mediated analgesia, this hypothetical system is resistant to tolerance.

Analgesics↗
PubMed1988

Benzodiazepine-induced hyperphagia: a test of the hunger-mimetic model.

The 'hunger-mimetic' model is a prominent explanatory account of benzodiazepine-induced hyperphagia. A salient feature of food deprivation (hunger) in laboratory animals is 'finicky' eating, or an enhanced reactivity to the palatability of food. If the hunger-mimetic model is correct, a similar finicky pattern of increased eating should be observed both in hungry (food-deprived) rats and in benzodiazepine-treated, hyperphagic rats. Two groups of rats were matched on measures of ad lib baseline intake of both a highly palatable food (sweetened condensed milk) and a food low in palatability (milk adulterated with 37.5 mg% quinine). Subsequently one group was placed on a moderate food deprivation schedule while the second group was maintained on ad lib food but was injected (IP) with 5 mg/kg chlordiazepoxide (CDP) 30 min prior to food presentation tests. Single-bottle tests indicated that while the food deprived animals exhibited a greater augmentation of eating when given the high-palatability food, the animals pretreated with CDP exhibited an indiscriminate elevation of eating across both foods. Similarly, on two-bottle choice tests the food-deprived rats exhibited an enhanced preference for the high-palatability food, whereas the CDP-treated animals did not change from baseline food preference. These results fail to support the hunger-mimetic model of benzodiazepine-induced hyperphagia. Alternative models based on a perseverative, disinhibitory action of benzodiazepines are discussed.

Animals↗
PubMed1987

The chronic effects of alcohol on memory. A contrast between a unitary and dual system approach.

Recent studies have indicated that impairment of memory is a common cognitive deficit related to long-term alcohol consumption. Such deficits range from subtle disturbance through a "subclinical" amnesic disorder to full-blown Korsakoff syndrome. This finding is congenial with the hypothesized continuum of alcohol-related impairment of memory. Among alcoholics, this memory impairment appears to be etiologically distinct from the commonly observed deficits in abstracting and problem-solving abilities. In the present chapter, a dual and a unitary formulation of memory are contrasted in their ability to present a coherent account of what memory tasks Korsakoff amnesics can and cannot do. The explanations offered by unitary theory are weak compared to those derived from the theory that memory consists of two distinct systems--experiential and abstractive memory. We indicate how the pattern of responding on standard clinical tests of memory can be coherently analyzed post hoc within the dual formulation. A number of experimental predictions are also presented based on the theory that Korsakoff amnesics have a profound impairment of experiential memory, whereas the abstractive system is essentially normal. Such experiments should clarify the nature both of Korsakoff amnesia and of memory itself. In conclusion, we indicated that memory disorders related to alcoholism can be understood in terms of a gradient, or continuum, of impairment of the experiential system.

Alcohol Amnestic Disorder↗
PubMed1986

Pavlovian conditioning and addictive behavior: relapse to oral self-administration of morphine.

The effect of conditional environmental stimuli on morphine consumption in rats was examined. Rats were first trained to consume a morphine solution (increased from 0.5 mg/ml to 1.2 mg/ml) by a forced drinking procedure spanning 235 days. Then, a period of abstinence of 81 days was given. They next received injections of morphine in one environment and injections of saline in a different environment (30 injections of morphine, dose increased from 5 mg/kg to 40 mg/kg). At the end of this phase, the effects of conditional environmental stimuli on tolerance to the analgesic effect of 40 mg/kg morphine were examined. Consistent with previous results, analgesic tolerance was most pronounced in the context of the cues previously associated with subcutaneous morphine injections. Finally, the effects of the different environments on consumption of morphine were determined in one-bottle and two-bottle tests. In a two-bottle test, there was almost no consumption of the morphine solution regardless of environment. In a one-bottle test, significantly more morphine was consumed in the drug environment than in the saline environment. The results are discussed in relation to theoretical views of the role of environmental stimuli in tolerance and drug dependence.

Administration, Oral↗
PubMed1984

Alcohol is an effective cue in the conditional control of tolerance to alcohol.

To assess the effectiveness of a pharmacological cue as a conditional stimulus in the Pavlovian model of drug tolerance, two groups of Wistar rats received equal numbers of IP injections of a low and a high dose of alcohol. One group (Paired) received a low dose (0.8 g/kg) of alcohol followed 60 min later by the high dose (2.5 g/kg). Another group (Unpaired) received the low and high doses on an unpaired basis. When tested for tolerance to the hypothermic effect of the high dose of alcohol, only the Paired group showed tolerance, and only if the low dose preceded the high. When a saline injection preceded the high dose injection, the Paired group showed a loss of tolerance. The Paired group also showed a compensatory hyperthermia following the low dose injection. Animals from the Paired group that received repeated administrations of the low dose followed by saline, showed a significant extinction effect as compared with animals that received repeated saline injections only. These findings support the Pavlovian model of conditional tolerance, extending the realm of effective conditional stimuli to include a low dose of a drug.

Animals↗
PubMed1984

A homeostatic model of Pavlovian conditioning: tolerance to scopolamine-induced adipsia.

Several experiments support a model proposing that tolerance to scopolamine-induced adipsia involves an interplay between processes of homeostatic regulation and Pavlovian conditioning. In Experiment 1a, rats given access to water while under the influence of scopolamine developed adipsic tolerance, whereas rats denied access to water in the drug state did not. In Experiment 1b, rats displayed adipsic tolerance only when scopolamine was administered with cues associated with previous drug injections. In Experiment 1c, adipsic-tolerant rats showed a polydipsic response to an injection of phenobarbital (which unconditionally augments water consumption) relative to nontolerant animals with the same pharmacological history. Experiment 2 assessed the effect of deprivation level on the Pavlovian extinction of adipsic tolerance. Rats satiated with water during extinction showed a loss of adipsic tolerance, whereas water-deprived rats did not. The present model is discussed in relation to (a) tolerance in other response systems such as morphine analgesia, (b) theories of extinction for nonpharmacological Pavlovian conditioning, and (c) homeostatic regulation and incentive motivation.

Animals↗
PubMed1982

Pavlovian conditional tolerance to haloperidol catalepsy: evidence of dynamic adaptation in the dopaminergic system.

An experiment with rats has demonstrated that Pavlovian conditioning factors determine the occurrence of tolerance to haloperidol catalepsy. Rats exhibited tolerance only in the environment previously associated with the drug. Previous research involving receptor binding techniques implicated an increase in the number of brain dopamine receptors as the mediator of neuroleptic tolerance. The present findings demonstrate that this change, by itself, cannot account for the conditional occurrence of such tolerance.

Animals↗
PubMed1982

Effects of pentobarbital and cocaine in rats expecting pentobarbital.

Rats received extensive exposure to pentobarbital in a distinctive environment, and were subsequently tested for tolerance to the sedative effects of pentobarbital either in the distinctive environment or in an environment previously associated only with saline. Rats tested when expecting pentobarbital (i.e., in the usual drug environment) were tolerant, but rats tested when not expecting the drug (i.e., in the saline environment) were not tolerant. These results extend demonstrations of conditional tolerance to the general behavioral arousal effects of a sedative hypnotic. Subsequently, the same rats were administered cocaine either when expecting pentobarbital or when not expecting pentobarbital. Rats administered cocaine when expecting pentobarbital exhibited more intense forms of cocaine-induced behavior than rats administered cocaine but not expecting pentobarbital. These results establish the phenomenon of conditional cross-potentiation between conditional drug states and unconditional drug-effects.

Animals↗
PubMed1981

Pavlovian control of cross-tolerance between pentobarbital and ethanol.

Tolerance to several effects of a number of drugs has been shown to depend on Pavlovian conditioning processes. Experiment I extended the compensatory conditioning model (Siegel 1975) to tolerance to the hypothermic effect of pentobarbital (30 mg/kg). In Experiment I, rats that acquired hypothermic tolerance in one environment did not display tolerance when tested in an environment not previously associated with drug administration. In Experiment II, rats were made tolerant to the hypothermic effect of pentobarbital (30 mg/kg) and tested for cross-tolerance to ethanol (2.5 g/kg). Cross-tolerance was observed, but it was significantly reduced if the test was in an environment different from the one in which tolerance to pentobarbital was originally acquired. Thus, the compensatory conditioning model accounts for at least part of the tolerance and cross-tolerance to the thermic effects of alcohol and pentobarbital. The physiological processes in the CNS underlying tolerance and cross-tolerance for these drugs, therefore, are controlled by associative processes.

Animals↗
PubMed1981

Sensitization to the behavioral effects of cocaine: modification by Pavlovian conditioning.

Sensitization to the behavioral effects of cocaine was more pronounced following drug administration in the presence of cues previously associated with cocaine administration than in their absence. Furthermore, sensitization was attenuated by repeated presentations of the usual predrug cues followed only by saline, i.e. sensitization was extinguishable. These findings indicate that Pavlovian conditioning contributes to sensitization, and have implications for treatment of stimulant abuse.

Animals↗
PubMed1981

Homeostatic regulation and Pavlovian conditioning in tolerance to amphetamine-induced anorexia.

A series of experiments on the role of Pavlovian processes in tolerance to amphetamine-induced anorexia in rats was conducted. In Experiment 1A, tolerance to the suppressant effect of d-amphetamine (4.0 mg/kg) on milk consumption was substantially diminished in an environment not previously associated with drug administration. Experiment 1B supported the interpretation that Pavlovian compensatory conditioning rather than a nonassociative mechanism mediated this phenomenon. Experiment 2 examined the hypothesis that "contingent tolerance" results from an inadvertent manipulation of Pavlovian cues. As in previous research, tolerance was contingent in that it did not develop if the rats were not exposed to food under the influence of the drug. Tolerance developed only if access to food occurred under the influence of amphetamine, but as in Experiment 1A, it was substantially diminished in an environment not previously associated with drug administration. Thus, tolerance to amphetamine-induced anorexia was shown to be both contingent on previous experience with food in the drugged state and subject to Pavlovian control. No current explanation for the occurrence of contingent tolerance or for the control of tolerance by Pavlovian processes can at once account for both of these findings. Experiment 3 confirmed the hypothesis that interaction with the food stimulus would be necessary to extinguish tolerance. This finding is also problematic for any current behavioral theory of tolerance. It is proposed that interaction with food is necessary for the homeostatic regulation of disturbances in eating caused by amphetamine. When activated, this regulatory process operates by means of Pavlovian conditional compensatory processes.

Animals↗
PubMed1979

Conditioned tolerance to the hypothermic effect of ethyl alcohol.

Results from experiments with rats support the proposition that tolerance to the hypothermic effect of alcohol involves the Pavlovian conditioning of compensatory responses. Tolerance was substantially reduced when alcohol was administered in an environment that had not been associated with alcohol. Direct evidence of a conditioned hyperthermic compensatory response was found.

Animals↗