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S T Tiffany

Publications and source records attributed to S T Tiffany.

50 records · Page 3Linked to original sources
PubMed1988

Tolerance to morphine in the rat: associative and nonassociative effects.

Two experiments were conducted to examine the impact of dose level and interdose interval (IDI) on the development of tolerance to the analgesic effect of morphine. In Experiment 1, rats were administered a series of low- (5 mg/kg) or high- (30 mg/kg) dose injections of morphine either explicitly paired or unpaired with a distinctive context at a 48-hr IDI. The development of tolerance following this regimen was assessed by shifts in dose-response curves to the right when animals were tested on a tail-flick device in the distinctive context. Only animals that had received morphine paired with the distinctive context were tolerant to morphine; the magnitude of this associative tolerance was a positive function of the level of the conditioning dose. In Experiment 2, rats were exposed to a high dose of morphine (30 mg/kg) either paired or unpaired with a distinctive context at one of two IDIs (24 or 96 hr). Tolerance testing revealed that at the long IDI, only associative tolerance was evident, whereas at the short IDI, tolerance in the unpaired condition was more pronounced with a corresponding decline in the development of associative tolerance. The relevance of these findings for psychological theories of drug tolerance are discussed. The overall pattern of results are consistent with the predictions of an habituation model of drug tolerance.

Animals↗
PubMed1987

The contribution of classical conditioning to tolerance to the antinociceptive effects of ethanol.

In rats, ethanol increases the latency of the tail-flick reflex to radiant heat. Three experiments examined the contribution of classical conditioning to the acquisition of tolerance to this antinociception. Experiment 1 showed that the antinociception produced by ethanol was dose dependent. The results of Experiment 2 demonstrated that rats exposed to a series of ethanol injections paired with a distinctive environment developed tolerance to this antinociception. In Experiment 3, tolerance was more pronounced in animals that had been exposed to ethanol and tested in the distinctive environment than in animals that had received ethanol in a nondistinctive environment. In contrast to previous reports in the literature, these results show that animals need not practice the tail-flick reflex while intoxicated in order to develop tolerance. Additionally, the data suggest that classical conditioning may contribute to tolerance to the antinociceptive effects of ethanol.

Analgesics↗
PubMed1986

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↗
PubMed1985

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↗
PubMed1983

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↗
PubMed1983

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↗
PubMed1981

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↗
PubMedDate not supplied

Dynorphin (1-13): analgesia, hypothermia, cross-tolerance with morphine and beta-endorphin.

Intracerebroventricular administration of 20, 40 and 60 nmol of dynorphin (1-13) produced analgesia, as assessed by flinch/jump response to footshock, and hypothermia in the rat. Rats developed tolerance to both the analgesic and thermic effects of the 20 nmol dose of dynorphin. Dynorphin and beta-endorphin showed cross-tolerance with respect to their analgesic but not their thermic effects. Dynorphin and morphine also produced cross-tolerant analgesic effects. Naloxone (10 mg/kg, IP) completely blocked the barrel rolling produced by 20 nmol dynorphin but did not alter its analgesic or thermic effects.

Analgesia↗
PubMedDate not supplied

Associative and nonassociative tolerance: the effects of dose and interdose interval.

Two experiments examined the effects of dose and interdose interval (IDI) on associative and nonassociative tolerance to morphine analgesia in rats. Associative contingencies were manipulated by administering low (5 mg/kg) or high (20 mg/kg) doses of morphine explicitly paired or unpaired with a distinctive context. Nonassociative processes were manipulated by administering morphine at a short (6-h) or long (96-h) IDI. Tolerance was assessed as shifts in morphine dose-response curves on the tail-flick test. Animals in the long IDI conditions showed considerable context-specific tolerance. Tolerance in the short IDI conditions was not influenced by contextual contingencies at the immediate test (Experiment 1) and showed no retention over a 30-day interval (Experiment 2), suggesting this tolerance was nonassociative. The impact of massed exposure to morphine and context on the disruption of learning at the short IDI is discussed.

Analgesics, Opioid↗