PMID- 9748096
DA - 19981209
DCOM- 19981209
LR - 20001218
IS - 0031-9384
VI - 64
IP - 3
DP - 1998 Jun 1
TI - Involvement of GABA(A) and GABA(B) receptors in the mediation of discriminative stimulus effects of gamma-hydroxybutyric acid.
PG - 293-302 AB - The present study was designed to further investigate the pharmacological profile of the discriminative stimulus effects of gamma-hydroxybutyric acid (GHB). Drugs acting at the gamma-aminobutyric acid (GABA)B receptor (baclofen and CGP 35348), GABA(A)/benzodiazepine receptor complex (diazepam), N-methyl-D-aspartate (NMDA) receptor complex (dizocilpine), and cannabinoid receptor (WIN 55,212-2) were tested for substitution or blockade of the GHB interoceptive cue in rats trained to discriminate either 300 or 700 mg/kg of GHB i.g. from water in a T-maze, food-reinforced drug discrimination paradigm. Baclofen completely substituted for both training doses of GHB; however, its potency in substituting for GHB increased as the training dose of GHB was increased. CGP 35348 partially and completely blocked the cue elicited by 300 and 700 mg/kg of GHB, respectively. In contrast, diazepam partially substituted for 300 mg/kg of GHB, while failing to produce a GHB-appropriate response in the rat group trained to the higher GHB dose. Neither dizocilpine nor WIN 55,212-2 substituted for GHB. Collectively, these data suggest that: a) GHB produces a compound stimulus; and b) GABA(B)- and GABA(A)-mediated cues are prominent components of the mixed stimulus of GHB. However, the quality (i.e., the proportion of the component cues) of the stimulus varies as the training dose of GHB is increased; indeed, the contribution of the GABA(A)- and GABA(B)-mediated cues were smaller and greater, respectively, at 700 and 300 mg/kg of GHB training doses.
[emd]
FAU - Colombo, G
AU - Colombo G
FAU - Agabio, R
AU - Agabio R
FAU - Lobina, C
AU - Lobina C
FAU - Reali, R
AU - Reali R
FAU - Gessa, G L
AU - Gessa GL
LA - eng
PT - Journal Article
CY - UNITED STATES
TA - Physiol Behav
JID - 0151504
RN - 0 (Anesthetics, Intravenous)
RN - 0 (GABA Agonists)
RN - 0 (GABA Antagonists)
RN - 0 (GABA Modulators)
RN - 0 (Organophosphorus Compounds)
RN - 0 (Receptors, GABA-A)
RN - 0 (Receptors, GABA-B)
RN - 1134-47-0 (Baclofen)
RN - 123690-79-9 (CGP 35348)
RN - 439-14-5 (Diazepam)
RN - 502-85-2 (Sodium Oxybate)
RN - 77086-22-7 (Dizocilpine Maleate)
SB - IM
MH - Anesthetics, Intravenous/*pharmacology
MH - Animal
MH - Baclofen/pharmacology
MH - Diazepam/pharmacology
MH - Discrimination (Psychology)/*drug effects
MH - Dizocilpine Maleate/pharmacology
MH - Dose-Response Relationship, Drug
MH - Food
MH - GABA Agonists/pharmacology
MH - GABA Antagonists/pharmacology
MH - GABA Modulators/pharmacology
MH - Male
MH - Organophosphorus Compounds/pharmacology
MH - Rats
MH - Receptors, GABA-A/agonists/antagonists & inhibitors/*physiology
MH - Receptors, GABA-B/agonists/antagonists & inhibitors/*physiology
MH - Reinforcement (Psychology)
MH - Sodium Oxybate/*pharmacology
MH - Support, Non-U.S. Gov't
EDAT- 1998/09/25
MHDA- 1998/09/25 00:01
AID - S0031938498000626 [pii]
PST - ppublish
SO - Physiol Behav 1998 Jun 1;64(3):293-302.