GABAB receptor stimulation decreases amphetamine-induced behavior and neuropeptide gene expression in the striatum.
The purpose of this study was to investigate whether GABA(B) receptor activation blocks acute amphetamine-induced behavioral activity, dopamine release, and neuropeptide mRNA expression in the striatum. Systemic administration of R-(+)-baclofen (1.25 mg/kg, i.p.) did not alter total distance traveled or vertical rearing induced by amphetamine (2.5 mg/kg, i.p.). At 2.5 mg/kg, baclofen did not alter spontaneous motor activity or total distance traveled, but completely blocked vertical rearing induced by amphetamine. At 5.0 mg/kg, baclofen completely blocked both total distance traveled and vertical rearing induced by amphetamine. Quantitative in situ hybridization histochemistry revealed that baclofen (2.5 mg/kg, i.p.) decreased the ability of amphetamine to increase preprodynorphin (PPD), preprotachykinin (PPT), preproenkephalin (PPE), and secretogranin II (SGII) mRNA levels in the striatum without altering the basal levels of these signals. Baclofen also blocked the amphetamine-induced rise in SGII mRNA in the core and shell of the nucleus accumbens and cingulate cortex. In a separate experiment, systemic baclofen (2.5 mg/kg) decreased the amphetamine-induced increase in dialysate dopamine levels in the striatum. These results suggest that reduced striatal dopamine release contributes to the ability of GABA(B) receptor activation to decrease acute amphetamine-induced behavioral activity and striatal neuropeptide gene expression.
Zhou
Wenxia
W
Department of Physiology and Neuroscience, Medical University of South Carolina, 173 Ashley Avenue, BSB 403, Charleston, SC 29425, USA.
Mailloux
Adam W
AW
Jung
Bruce J
BJ
Edmunds
Hayward S
HS
McGinty
Jacqueline F
JF
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D058786:GABA-B Receptor Agonists; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009479:Neuropeptides / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000378:metabolism*
D058786:GABA-B Receptor Agonists; D009479:Neuropeptides; D012333:RNA, Messenger; D018080:Receptors, GABA-B; D000661:Amphetamine; D001418:Baclofen