Inactivation of the bed nucleus of the stria terminalis in an animal model of relapse: effects on conditioned cue-induced reinstatement and its enhancement by yohimbine.
BACKGROUND
Drug-associated cues and stress increase craving and lead to greater risk of relapse in abstinent drug users. Animal models of reinstatement of drug seeking have been utilized to study the neural circuitry by which either drug-associated cues or stress exposure elicit drug seeking. Recent evidence has shown a strong enhancing effect of yohimbine stress on subsequent cue-elicited reinstatement; however, there has been no examination of the neural substrates of this interactive effect.


OBJECTIVE
The current study examined whether inactivation of the bed nucleus of the stria terminalis (BNST), an area previously implicated in stress activation of drug seeking, would affect reinstatement of cocaine seeking caused by conditioned cues, yohimbine stress, or the combination of these factors.


METHODS
Male rats experienced daily IV cocaine self-administration, followed by extinction of lever responding in the absence of cocaine-paired cues. Reinstatement of responding was measured during presentation of cocaine-paired cues, following pretreatment with the pharmacological stressor, yohimbine (2.5 mg/kg, IP), or the combination of cues and yohimbine.


RESULTS
All three conditions led to reinstatement of cocaine seeking, with the highest responding seen after the combination of cues and yohimbine. Reversible inactivation of the BNST using the gamma-aminobutyric acid receptor agonists, baclofen + muscimol, significantly reduced all three forms of reinstatement.


CONCLUSIONS
These results demonstrate a role for the BNST in cocaine seeking elicited by cocaine-paired cues, and suggest the BNST as a key mediator for the interaction of stress and cues for the reinstatement of cocaine seeking.
Buffalari
Deanne M
DM
Department of Neuroscience, University of Pittsburgh, Pittsburgh, PA 15260, USA.
See
Ronald E
RE
D000818:Animals; D001418:Baclofen / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology; D019970:Cocaine-Related Disorders / Q000503:physiopathology* / Q000517:prevention & control*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D004359:Drug Therapy, Combination; D005108:Extinction, Psychological / Q000187:drug effects*; D008297:Male; D023421:Models, Animal; D009118:Muscimol / Q000008:administration & dosage / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D055502:Secondary Prevention; D012646:Self Administration / Q000379:methods; D012686:Septal Nuclei / Q000187:drug effects / Q000502:physiology*; D015016:Yohimbine / Q000494:pharmacology*
D009118:Muscimol; D015016:Yohimbine; D001418:Baclofen; D003042:Cocaine
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