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Biomedical subjects

T B Baker

Publications and source records attributed to T B Baker.

At least 55 records · Page 3Linked to original sources

Endogenous analgesia in the pregnant rat: an artifact of weight-dependent measures?

It has been reported that pregnancy produces an opioid-mediated, endogenous analgesia in the rat. In an attempt to confirm this finding, we used 5 different analgesic measures to compare the responsiveness of pregnant and non-pregnant female rats to painful stimuli. Pregnant and non-pregnant rats differed only when assessed by measures that were highly correlated with body weight. Furthermore, the reduced pain responsiveness of pregnant rats was not prevented by administration of the opioid antagonists, naloxone or naltrexone. We can find no evidence for an endogenous analgesia of pregnancy; instead, our results suggest that findings of a diminished response to painful stimuli in pregnant rats may be an artifact related to the greater body mass/weight of the pregnant animals.

Animals↗

The motivation to use drugs: a psychobiological analysis of urges.

Traditionally, theories of addiction have stressed that drug urges are characterized by dysphoria, occur in response to decreasing levels of drug or drug effect, and are associated with withdrawal symptoms/signs or drug-antagonistic responses arising from a homeostatic mechanism. However, recent research has shown that urges, drug self-administration, and relapse all occur concomitant with both positive and negative affect, rising and falling levels of drug, and with drug-agonistic responses, as well as antagonistic/withdrawal responses. In keeping with recent theorizing about motivation and emotions, we believe that affective responding provides a readout of the motivational status of an organism (e.g., Buck, 1985). We conceive of urges as affects, whose activation mediates drug pursuit and self-administration. Moreover, we believe that affects are represented in neural networks comprising information on affect-relevant stimuli, responses, and meaning/expectancy. We believe that there are two types of urge networks. One, a "positive-affect" network, is activated, associatively and nonassociatively, by appetitive stimuli, especially appetitive drug actions that activate "GO" motivational incentive systems. Activation of this network is characterized by positive affect, drug isodirectional responding, attentional focus on a dominant response, and enhanced pursuit of appetitive stimuli--especially the drug. The operating characteristics of the positive-affect network, and the associated motivational systems, result in a drug's instating a positive feedback loop. Appetitive drug actions increase the likelihood of the pursuit of appetitive stimuli, and additional drug constitutes a prepotent candidate from among the available appetitive stimuli. This positive feedback loop may account in part for cardinal features of addiction: for example, the great relapse likelihood once any drug is sampled, the attainment of very high blood levels of a drug, and the pursuit of adjunctive appetitive stimuli while using a drug. The second type of urge network we have labeled a "negative-affect" network, and we believe it is activated, associatively and nonassociatively, by inappetitive stimuli or consequences (punishment, signals of punishment, frustrating lack of reward, etc.) and by withdrawal and signals of withdrawal (e.g., drug cues, which during the course of addiction are associated with both direct drug effects and withdrawal). Activation of the network is characterized by withdrawal symptoms and signs, negative affect, and drug seeking.(ABSTRACT TRUNCATED AT 400 WORDS)

Adaptation, Psychological↗

Influence of stress on morphine-induced hyperthermia: relevance to drug conditioning and tolerance development.

Controversy exists regarding (a) whether rats become tolerant, or sensitized, to morphine-induced hyperthermia and (b) the directionality of the conditioned pyretic effects of morphine. In these studies, stress produced by temperature-assessment procedures affected rats' pyretic response to morphine. Under conditions of high stress, rats first showed diminished, and then enhanced, hyperthermic responding across repeated morphine dosing (5 or 35 mg/kg). The diminished hyperthermia can be attributed to habituation to high levels of assessment stress. Repeated morphine doses delivered under conditions of low stress produced only enhanced hyperthermic responding, which indicates that rats become sensitized to morphine's hyperthermic effects. There was little evidence that morphine supported conditioning of pyretic responses. Finally, the temperature-assessment stress that produced hyperthermia was mediated by opiate peptides, was blocked by naloxone, and enhanced the agonist effects of morphine. The relevance of these findings to theories of drug conditioning and tolerance is discussed.

Animals↗

Drug signals enhance morphine tolerance development in hypophysectomized rats.

Hypophysectomized and sham-operated (normal) rats were given morphine (5 mg/kg) either paired or unpaired with distinctive environmental cues. Both hypophysectomized and normal animals developed analgesic tolerance when drug effects were signaled, but little tolerance was evident in either surgery group when drug was unsignaled. Results suggest that the pituitary is not critical to associational tolerance development.

Animals↗

Conditioned morphine tolerance in the rat: absence of a compensatory response and cross-tolerance with stress.

In four separate experiments with rats as subjects, strong evidence was obtained that tolerance development to morphine analgesia occurs most rapidly when morphine delivery is paired with salient contextual cues. However, contextual cues previously paired with morphine did not elicit conditioned drug-compensatory responses when presented to nondrugged animals. These results were obtained by different analgesia assessments, with different drug-administration--analgesia-test latencies, and in environments differing with respect to stress level. Stress level did influence nociceptive response, as it was found that the combination of bright illumination, white noise, and a strong odor resulted in antinociception in the absence of drug. Moreover, rats that had a history of receiving morphine in this stressful context were tolerant to this stress-induced antinociception, but only when morphine was present in their systems. In the final two studies, this antinociception, which was cross-tolerant with morphine, was characterized with respect to naloxone reversibility and brain levels of met- and leu-enkephalin as determined by radioimmunoassay.

Animals↗

Alcohol dependence and taste-mediated learning in the rat.

Alcohol dependence and taste-mediated learning were investigated in the rat using intubation procedure to produce dependence, an experimenter-controlled conditioned stimulus (CS) flavor infusion procedure, and behavioral criteria to assign conditioning alcohol dosage. Stress produced by the experimental procedures (e.g., handling, stomach distention) produced flavor aversions, and these aversions were attenuated by small alcohol doses. When stress was reduced and made less associable with the flavor CS, alcohol dependence, by itself, did not protect against the development of alcohol-induced taste aversions. Alcohol withdrawal produced aversions for an associated flavor, but these aversions were attenuated by pairing the flavor with small doses of alcohol. Thus, the relief of alcohol withdrawal illness did not produce preferences for associated flavors, but it did protect against the development of taste aversions.

Alcoholism↗

Alcohol and taste-mediated learning.

Taste-mediated learning is relevant to the alcohol consumption patterns of animals. This review concludes that taste aversion learning has thus far prevented development of an animal model of alcoholism. The presence of a taste cue, lack of control over alcohol administration, and high alcohol concentrations or dosages all facilitate the development of alcohol aversions. There is little evidence that taste preference learning is involved in the development of alcohol dependence. Data from taste-mediated learning research with animals are consistent with drinking patterns of human alcoholics.

Alcohol Drinking↗

Morphine tolerance in rats: congruence with a Pavlovian paradigm.

Evidence for associational and nonassociational mechanisms of tolerance development was found in four experiments using an automated flinch/jump assessment of morphine's analgesic effects. Rats receiving morphine in a distinctive environment displayed greater tolerance when tested in that environment than animals receiving equal but unpaired exposure to the drug and environment. This context effect occurred at low (5 mg/kg) and moderate (20 mg/kg) doses and was attenuated by predrug exposure to the tolerance-test environment. This attenuation was found to be due to latent inhibition rather than to stress induction or novelty reduction. In general, results of this series of experiments support a Pavlovian model of contextually mediated tolerance and are inconsistent with other explanations.

Animals↗

Potentiation of ethanol withdrawal by prior dependence.

Thirty rats were randomly assigned to three groups. Group 1 was given a 21-day exposure to an ethanol (EtOH) liquid diet, while Groups 2 and 3 were given equivalent amounts of an isocaloric non-EtOH liquid diet. Group 1 rats had withdrawal syndromes following EtOH removal. After a two-week recovery period, Groups 1 and 2 were both exposed to an EtOH diet, while Group 3 again received an isocaloric non-EtOH liquid diet. Groups 1 and 2 were withdrawn after 12 days of EtOH exposure and were rated with a behavioral withdrawal rating scale, for which interobserver reliability estimates were determined. Previously dependent (Group 1) rats showed more severe withdrawal syndromes, including a higher incidence of seizures, than rats undergoing their initial withdrawal (Group 2). Studies that do not agree with this finding are discussed.

Alcoholism↗