GABAB 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 both neurotransmitters is influenced by GABAB metabotropic receptors for the principal inhibitory neurotransmitter GABA. Accordingly, GABAB receptors were 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 density was not altered at either time. Baclofen-mediated [S-35]GTP gammaS binding, however, was selectively augmented in the prefrontal cortex and attenuated in the nucleus accumbens at 14 days, but not one day, after amphetamine treatment. Changes in GABAB receptor coupling to G-proteins in rats sensitized to amphetamine, but not in similarly treated but unsensitized rats, lead us to suggest that altered GABAB receptor functioning may contribute to the expression of amphetamine-induced behavioral sensitization. (C) 2000 IBRO. Published by Elsevier Science Ltd. All rights reserved.