guanosine-5--o-(3-thiotriphosphate) and Amphetamine-Related-Disorders

Modified dopamine and glutamate neurotransmission in discrete brain regions is implicated in stimulant-induced behavioral sensitization. Release of both neurotransmitters is influenced by GABA(B) metabotropic receptors for the principal inhibitory neurotransmitter GABA. Accordingly, GABA(B) receptors were examined in rats sensitized to amphetamine by measuring receptor density and coupling to G-proteins indicated as [(3)H]baclofen binding and baclofen-mediated [(35)S]GTP gamma S binding. Repeated treatment with (+)-amphetamine (5mg/kg per day, i.p., for five days) sensitized the rats to amphetamine challenge (1mg/kg) at 14 days, but not one day, later. GABA(B) receptor density was not altered at either time. Baclofen-mediated [(35)S]GTP gamma S 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 GABA(B) receptor coupling to G-proteins in rats sensitized to amphetamine, but not in similarly treated but unsensitized rats, lead us to suggest that altered GABA(B) receptor functioning may contribute to the expression of amphetamine-induced behavioral sensitization.

Topics: Amphetamine; Amphetamine-Related Disorders; Animals; Baclofen; Dopamine; Drug Administration Schedule; Glutamic Acid; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Male; Motor Activity; Nucleus Accumbens; Prefrontal Cortex; Radioligand Assay; Rats; Rats, Sprague-Dawley; Receptors, GABA-B; Sulfur Radioisotopes