Conditioned drug effects and absence of tolerance to d-amphetamine induced motor activity

Tilson, Hugh A.; Rech, Richard H.

doi:10.1016/0091-3057(73)90091-9

Cited by 212 publications

(84 citation statements)

References 16 publications

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“…In the present study, rats were tested for psychomotor sensitization in the selfadministration environment, while in the previous study, rats were tested in a different environment never paired with cocaine effects. Since psychomotor sensitization is exquisitely sensitive to the environmental context (Tilson and Rech, 1973;Stewart and Vezina, 1991;Ahmed et al, 1993), the different outcome between the two studies may suggest that psychomotor sensitization to cocaine in LgA rats is more sensitive to contextual shifts than in ShA rats. Future experiments are needed to test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

“…This procedure allowed both within-and betweensubjects assessments of psychomotor sensitization. Second, the stimulant effects of cocaine were measured in the environment paired with cocaine self-administration, thereby preserving the well-documented environmental specificity of psychomotor sensitization (Tilson and Rech, 1973;Stewart and Vezina, 1991;Ahmed et al, 1993). Finally, we compared the efficacy of cocaine to induce concurrently locomotion and reinstatement of drug-seeking behavior during the maintenance of escalated levels of cocaine selfadministration.…”

Section: Introductionmentioning

confidence: 99%

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Dissociation of Psychomotor Sensitization from Compulsive Cocaine Consumption

Ahmed¹,

Cador²

2005

Neuropsychopharmacol

146

143

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The transition from drug use to drug addiction is associated with a process of escalation, whereby drug use becomes excessive and difficult to control. Several mechanisms have been advanced to explain escalating patterns of drug use as opposed to nonescalating patterns. Although current evidence favors hedonic tolerance, there remains some dispute about the contribution of behavioral sensitization to cocaine intake escalation. Here, we concurrently assessed the ability of cocaine to induce psychomotor sensitization and drug-seeking behavior in animals with 1-h (short access or ShA) vs 6-h (long access or LgA) access to intravenous (i.v.) cocaine selfadministration. As expected, cocaine intake by LgA rats escalated over time and became excessive compared to cocaine intake by ShA rats, which remained low and stable. Despite escalated levels of cocaine consumption, however, LgA rats were not more sensitized to cocaine than ShA rats. The dose-effect function for cocaine-induced locomotion (0.125-1 mg, i.v.) was shifted to the left in LgA rats by the same amount as in ShA rats after cocaine self-administration. In contrast, LgA rats were much more responsive than ShA rats to the motivational effects of cocaine, as measured by the ability of i.v. cocaine to reinstate extinguished drug-seeking behavior. This study demonstrates a dissociation of psychomotor sensitization from the change in motivation underlying the transition to compulsive cocaine consumption, and therefore suggests that responsiveness to the motivational effects of the drug, not psychomotor sensitization, would represent a specific behavioral marker of the transition to and maintenance of compulsive cocaine use.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Dissociation of Psychomotor Sensitization from Compulsive Cocaine Consumption

Ahmed¹,

Cador²

2005

Neuropsychopharmacol

146

143

View full text Add to dashboard Cite

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“…One of these is a conditioned facilitation, resulting from the Pavlovian pairing of the context and drug, which produces a conditional response to drug-associated cues. This can add to the sensitized response in the drug-paired context [38,39]. The other is an occasion-setting mechanism that prevents the expression of sensitisation in the environment where the drug is not expected but enhances the expression of sensitisation in the context where the drug is expected [2,37].…”

Section: Learning Processes Governing Amphetamine Sensitizationmentioning

confidence: 99%

“…There are two learning processes by which psychostimulant behavioral sensitization can be modified: (i) An occasion-setting mechanism [2,37] can prevent the expression of behavioral sensitization in contexts in which the drug is not expected. (ii) Excitatory Pavlovian associations can increase drug-induced psychomotor response when animals are placed in environments where the drug is expected [2,38,39]. These two associative processes may combine to modulate the expression of sensitization [2,3].…”

Section: Introductionmentioning

confidence: 99%

Histone deacetylase inhibitors modulates the induction and expression of amphetamine-induced behavioral sensitization partially through an associated learning of the environment in mice

Kalda

Heidmets

Shen

et al. 2007

Behavioural Brain Research

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The behavioral sensitization produced by repeated amphetamine treatment may represent the neural adaptations underlying some of the features of psychosis and addiction in humans. Chromatin modification (specifically histone hyperacetylation) was recently recognized as an important regulator of psychostimulant-induced plasticity. We have investigated the effects of treatment with the histone deacetylase (HDAC) inhibitors butyric acid (BA, 630 mg/kg, i.p) and valproic acid (VPA, 175 mg/kg, i.p.) on the psyhcostimulant locomotor sensitization induced by amphetamine (AMPH, 2.0 mg/kg, i.p.). Neither BA nor VPA had locomotor effects alone, but both significantly potentiated the amphetamine-induced behavioral sensitization in mice. At the molecular level, VPA and amphetamine produced an increase of histone H4 acetylation in the striatum as detected by Western blot analysis, while co-treatment with VPA and AMPH produced an additive effect on histone H4 acetylation. We then administered the HDAC inhibitors after treatment with amphetamine for 8 days to establish locomotor sensitization. We found that repeated administration of VPA or BA for 6 days inhibited the expression of sensitized response following amphetamine challenge. Finally, in a context-specific model we studied the effect of HDAC inhibitors on amphetamine-induced association of the treatment environment (associative learning). We found that VPA and BA enhance the context-specificity of expression of amphetamine sensitization. Thus, HDAC inhibitors differentially modulate the induction and expression of amphetamine-induced effects. Together, these results suggest that dynamic changes in chromatin modification may be an important mechanism underlying amphetamine-induced neuronal plasticity and associative learning.

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“…When cocaine injections are given in the same environment where the locomotor effects of cocaine are to be subsequently tested, maximal evidence of cocaine sensitization is seen; when cocaine injections are given repeatedly in the home cage they cause substantially less sensitization to cocaine subse quently given in distinct test chambers (Jackson and Nutt, 1993;Post et al, 1981;Weiss et a l, 1989). Thus, a portion of the augmented locomotor response seen after repeated stimulant injections is due to a conditioned associationpresumably involving Pavlovian conditioning (Tilson and Rech, 1973) -between the drug and the environment in which it is given (Stewart and Eikelboom, 1987).…”

Section: Introductionmentioning

confidence: 99%

Influence of novel and habituated testing conditions on cocaine sensitization

Wise

Gingras

Amit

1996

European Journal of Pharmacology

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Female Swiss-Webster mice were treated daily for 10 days with cocaine (15 m g/kg i.p.) followed by 10 days with saline or ethanol (1.6 g /kg i.p.) or the reverse; following each injection in the experimental conditions locomotion was quantified in photocell cages. In animals given cocaine first, cocaine-induced locomotion was initially high and did not increase further with successive injections. In animals given prior saline or ethanol treatments, cocaine-induced locomotion was initially low but increased with successive cocaine treatments, There was no evidence of sensitization to the locomotor-stimulating effects of ethanol or of cross-sensitization between ethanol and cocaine. With respect to subsequent cocaine sensitization, the essential feature of prior saline or ethanol treatment appeared to be the handling and injection experience itself; a control group receiving prior saline injections in the home cage also showed a low level of cocaine-induced locomotion on the first day of cocaine testing but increasing locomotion with repeated cocaine testing. Thus, cocaine sensitization, rather than a progressive augmentation of motor function, may reflect a progressive reversal of the behavioral suppression caused by habituation to aspects of the testing situation or to some form of situational anxiety that precludes normal exploratory responses.

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Conditioned drug effects and absence of tolerance to d-amphetamine induced motor activity

Cited by 212 publications

References 16 publications

Dissociation of Psychomotor Sensitization from Compulsive Cocaine Consumption

Dissociation of Psychomotor Sensitization from Compulsive Cocaine Consumption

Histone deacetylase inhibitors modulates the induction and expression of amphetamine-induced behavioral sensitization partially through an associated learning of the environment in mice

Influence of novel and habituated testing conditions on cocaine sensitization

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