Discriminative stimulus effects of GHB and GABA(B) agonists are differentially attenuated by CGP35348.
The aim of this study was to examine the possible heterogeneity of mechanisms that contribute to the discriminative stimulus and rate-decreasing effects of gamma-hydroxybutyrate (GHB). Dose effect curves were determined for GHB and two GABA(B) receptor agonists (baclofen and SKF97541) alone and together with the selective GABA(B) receptor antagonist CGP35348 in rats discriminating GHB. In a second study, GHB and SKF97541 dose effect curves were determined alone and together with baclofen. CGP35348 attenuated the discriminative stimulus and rate-decreasing effects of SKF97541 and baclofen to a greater extent than those of GHB. In the second study, baclofen enhanced the discriminative stimulus and rate-decreasing effects of GHB and SKF97541; however, the GHB dose effect curve was not shifted in a parallel manner. Taken together, these data suggest that multiple mechanisms, possibly including GHB receptors and GABA(B) receptor subtypes, are involved in the discriminative stimulus and rate-decreasing effects of GHB.
Carter
Lawrence P
LP
Department of Pharmacology, The University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, Texas 78229, USA.
Chen
Weibin
W
Coop
Andrew
A
Koek
Wouter
W
France
Charles P
CP
D000704:Analysis of Variance; D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D004193:Discrimination Learning / Q000187:drug effects*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D018755:GABA Agonists / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D008297:Male; D009943:Organophosphorus Compounds / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012978:Sodium Oxybate / Q000494:pharmacology*
D018755:GABA Agonists; D018756:GABA Antagonists; D058786:GABA-B Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009943:Organophosphorus Compounds; C068457:3-aminopropyl(methyl)phosphinic acid; D012978:Sodium Oxybate; C066430:CGP 35348; D001418:Baclofen