Intravenous heroin self-administration decreases GABA efflux in the ventral pallidum: an in vivo microdialysis study in rats.
Several lines of evidence suggest that opiate-induced disinhibition of the ventral pallidum participates in the mediation of opiate reward, though direct in vivo evidence to support this hypothesis has been lacking. The present experiment tested this hypothesis by investigating alterations in ventral pallidal amino acid efflux using in vivo microdialysis during ongoing intravenous heroin self-administration in rats. Concentrations of the inhibitory amino acid GABA in ventral pallidal dialysates were significantly reduced within the first 10 min of heroin self-administration (0.02 mg per infusion; FR-1), and remained approximately 65% of presession baseline levels for the remainder of the 3-h self-administration session. Dialysate glutamate levels were unaltered during the first hour of heroin intake but significantly increased to a stable level of approximately 120% presession values during the subsequent 2 h of self-administration. Thus, heroin self-administration is associated with both decreased GABA efflux and a late phase increase in glutamate efflux in the ventral pallidum. These observations are consistent with the hypothesis that heroin self-administration results in a disinhibition and/or excitation of the ventral pallidum.
Caillé
Stéphanie
S
Department of Neuropharmacology, CVN-7, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Parsons
Loren H
LH
D000818:Animals; D001522:Behavior, Animal; D001923:Brain Chemistry; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D003932:Heroin / Q000008:administration & dosage* / Q000494:pharmacology; D007262:Infusions, Intravenous / Q000379:methods; D008297:Male; D017551:Microdialysis / Q000379:methods*; D051381:Rats; D017208:Rats, Wistar; D012055:Reinforcement Schedule; D012646:Self Administration / Q000379:methods; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid; D003932:Heroin