Both GABA(B) receptor agonist and antagonists decreased brain stimulation reward in the rat.
The present experiments were designed to determine the role of GABA(B) receptor function on brain stimulation reward. Using a discrete-trial current-intensity threshold procedure, dose-effect functions were generated for the GABA(B) receptor agonist CGP 44532 (0-1.0 mg/kg, s.c.) and the GABA(B) receptor antagonists CGP 56433A (0-10.0 mg/kg, s.c.) and CGP 51176 (0-300.0 mg/kg, s.c.) on brain reward thresholds in rats. The GABA(B) receptor antagonists CGP 56433A and CGP 51176 were used also to examine interaction effects with the GABA(B) receptor agonist CGP 44532 on reward thresholds. Administration of the highest doses of both the GABA(B) receptor agonist and antagonists elevated reward thresholds. Thus, both the agonist and antagonists used induced a reward decrement when administered separately. In addition, the co-administration of either of the two receptor antagonists with the agonist induced an additive effect on thresholds, rather than blocking the agonist-induced threshold elevations. These results suggest that activation of GABA(B) receptors modulates intracranial self-stimulation behavior in a complex fashion, possibly through differential effects of GABA(B) agonists and antagonists on pre- and post-synaptic GABA(B) receptors.
Macey
D J
DJ
Department of Neuropharmacology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. dmacey@scripps.edu
Froestl
W
W
Koob
G F
GF
Markou
A
A
D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D001921:Brain / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology*; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008297:Male; D010721:Phosphinic Acids / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012201:Reward; D012653:Self Stimulation; D005680:gamma-Aminobutyric Acid / Q000031:analogs & derivatives / Q000494:pharmacology
C112036:3-amino-2-(S)-hydroxypropyl-methyl-phosphinic acid; D001565:Benzoates; D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D010721:Phosphinic Acids; C105509:(3-(1-((3-(cyclohexylmethyl)hydroxyphosphinyl)-2-hydroxypropyl)amino)ethyl)benzoic acid; D005680:gamma-Aminobutyric Acid