GABA(B) receptors: Altered coupling to G-proteins in rats sensitized to amphetamine

Modified dopamine and glutamate neurotransmission in discrete brain regions is implicated in stimulant-induced behavioral sensitization. Release of bo th neurotransmitters is influenced by GABAB metabotropic receptors for the principal inhibitory neurotransmitter GABA. Accordingly, GABAB receptors we re examined in rats sensitized to amphetamine by measuring receptor density and coupling to G-proteins indicated as [H-3]baclofen binding and baclofen -mediated [S-35]GTP gammaS binding. Repeated treatment with (+)-amphetamine (5 mg/kg per day, i.p., for five days) sensitized the rats to amphetamine challenge (1 mg/kg) at 14 days, but not one day, later. GABAB receptor dens ity was not altered at either time. Baclofen-mediated [S-35]GTP gammaS bind ing, however, was selectively augmented in the prefrontal cortex and attenu ated in the nucleus accumbens at 14 days, but not one day, after amphetamin e treatment. Changes in GABAB receptor coupling to G-proteins in rats sensitized to amph etamine, but not in similarly treated but unsensitized rats, lead us to sug gest that altered GABAB receptor functioning may contribute to the expressi on of amphetamine-induced behavioral sensitization. (C) 2000 IBRO. Publishe d by Elsevier Science Ltd. All rights reserved.