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Neurochemical correlates of relapse to d-amphetamine self-administration by rats induced by stimulation of the ventral subiculum

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Abstract

Rationale and objectives

Previous studies show that electrical stimulation of the ventral subiculum (vSub) can reinstate drug-seeking behavior in rats following extinction. This study examined whether vSub stimulation could also evoke reinitiation of d-amphetamine (d-AMPH) self-administration during voluntary abstinence following a prolonged bout of drug intake. Dynamic changes in extracellular levels of dopamine (DA) and metabolites in the nucleus accumbens (NAc) during 48-h unlimited access to d-AMPH by rats were monitored. Neurochemical correlates of relapse to d-AMPH administration induced by vSub stimulation or by experimenter administered d-AMPH infusions were also examined during voluntary abstinence in separate experiments.

Methods and results

In vivo microdialysis using high-pressure liquid chromatography with electrochemical detector (HPLC-EC) was used to monitor changes in DA and metabolite efflux in the NAc during a continuous access-abstinence-relapse cycle of d-AMPH self-administration in a 48-h test. The initial pattern of drug intake was associated with significant increases in DA efflux in the NAc. During the abstinence phase, DA efflux was near pre-session baseline values. Electrical stimulation at the vSub after 2 h of abstinence immediately induced a significant increase in DA efflux and reinstatement of drug self-administration behavior. Evoked DA release and responses on drug-paired lever induced by vSub stimulation were significantly greater than those induced by experimenter-administered d-AMPH.

Conclusions

Relapse to drug-taking behavior can be triggered by activation of the subicular glutamatergic pathway to the NAc. This study also confirmed that during abstinence the neurochemical response of the mesolimbic DA system to d-AMPH is attenuated and this can be reversed by vSub stimulation.

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Acknowledgements

This research was supported by a grant from the Canadian Institutes of Health Research. P.T. was supported by a Royal Thai Government Graduate Fellowship. We gratefully acknowledge Dr. Patricia Di Ciano for teaching IVSA techniques and Fred LePiane, Christina Cheng and Niwat Taepavarapruk for their assistance.

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  1. Department of Psychiatry, University of British Columbia, 2255 Westbrook Mall, Vancouver, BC, Canada, V6T 2A1

    Pornnarin Taepavarapruk & Anthony G. Phillips

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  1. Pornnarin Taepavarapruk
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  2. Anthony G. Phillips
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Correspondence to Anthony G. Phillips.

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Taepavarapruk, P., Phillips, A.G. Neurochemical correlates of relapse to d-amphetamine self-administration by rats induced by stimulation of the ventral subiculum. Psychopharmacology 168, 99–108 (2003). https://doi.org/10.1007/s00213-002-1337-2

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  • DOI: https://doi.org/10.1007/s00213-002-1337-2

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