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 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.
Zhang
K
K
Mailman Research Center, McLean Division of Massachusetts General Hospital, 115 Mill Street, Belmont, MA 02478, USA. kz@mclean.harvard.edu
Tarazi
F I
FI
Campbell
A
A
Baldessarini
R J
RJ
D000661:Amphetamine / Q000494:pharmacology*; D019969:Amphetamine-Related Disorders / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004298:Dopamine / Q000378:metabolism; D004334:Drug Administration Schedule; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009714:Nucleus Accumbens / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism*; D013462:Sulfur Radioisotopes
D018080:Receptors, GABA-B; D013462:Sulfur Radioisotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D018698:Glutamic Acid; D000661:Amphetamine; D019204:GTP-Binding Proteins; D001418:Baclofen; D004298:Dopamine