d-Amphetamine ”cue” generalizes to social defeat stress: behavioral sensitization and attenuated accumbens dopamine (original) (raw)

Abstract

Rationale: Psychomotor stimulant drugs engender intense euphoria as well as anxiogenic effects, both potentially involving the mesolimbic dopamine system. Objectives: (1) Do animals that discriminate a psychomotor stimulant drug from saline generalize to a non-pharmacological stressful event such as social defeat? (2) How does the generalization from _d-_amphetamine to social defeat stress relate to dopamine overflow in the mesocorticolimbic system in response to this stress? Methods: Adult male Long-Evans rats were trained to discriminate either 1.0 mg/kg _d-_amphetamine or 10 mg/kg cocaine from saline in a two-lever drug discrimination task; each injection-appropriate tenth lever press was reinforced by milk presentation (fixed ratio, FR10). After confirming systematic cocaine and _d-_amphetamine dose-effect curves, additional discrimination tests involved exposure to several stress conditions; (1) brief confrontations with an aggressive resident rat that resulted in the intruder’s defeat. Rats were administered saline, then exposed to aggressive threats behind a protective screen for 15 min, and subsequently performed the two-lever discrimination task; (2) exposure for 15 min to aggressive threats without prior defeat; (3) exposure to a novel cage for 15 min. A subgroup of rats was prepared for in vivo microdialysis after they generalized the social stress response to the _d-_amphetamine cue. Results: Nine of 35 _d_-amphetamine-trained and six of 18 cocaine-trained animals responded at least 80% at the drug-appropriate lever after social defeat stress. Social defeat stress increased dopamine in nucleus accumbens, with a closely similar dopamine response in amphetamine-discriminating rats that were behaviorally sensitized versus those that were not sensitized by amphetamine. Conclusions: Generalization from social stress to the stimulant ”cue” differs among individuals, which may be relevant to the anxiety-like effects of stimulants. By contrast, mesolimbic DA activity and motor activity was increased in response to social defeat stress or a _d-_amphetamine challenge, regardless of the qualitatively different stimulant-stress generalization. Mesolimbic DA in response to stress or amphetamine appears significant in behavioral activation, but not in the qualitatively divergent internal stimulus properties.

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Authors and Affiliations

  1. Department of Psychiatry and Pharmacology, Tufts University, Medford and Boston, Massachusetts, USA, , , , , , US
    K. A. Miczek
  2. Department of Psychology, Tufts University, Medford and Boston, Massachusetts, USA, , , , , , US
    N. H. Mutschler, A.M.M. van Erp, A. D. Blank & S. C. McInerney

Authors

  1. K. A. Miczek
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  2. N. H. Mutschler
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  3. A.M.M. van Erp
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  4. A. D. Blank
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  5. S. C. McInerney
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Received: 1 March 1999 / Final version: 17 June 1999

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Miczek, K., Mutschler, N., van Erp, A. et al. _d_-Amphetamine ”cue” generalizes to social defeat stress: behavioral sensitization and attenuated accumbens dopamine.Psychopharmacology 147, 190–199 (1999). https://doi.org/10.1007/s002130051160

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