Methylxanthine discrimination in the rat: possible benzodiazepine and adenosine mechanisms.
Rats were trained to discriminate either caffeine or theophylline from saline using a two-lever discrimination paradigm. Since methylxanthines have been found to interfere with agonist binding at both adenosine and benzodiazepine (BDZ) receptors, chlordiazepoxide (CDP) and L-PIA (an adenosine analog) were tested for generalization to and blockade of both xanthine cues. Neither L-PIA nor CDP generalized to either xanthine cue, although both produced dose-related decreases in response rate. CDP, but not L-PIA, produced dose-related decreases in drug-lever responses when combined with training doses of caffeine or theophylline. Response rates indicated a complex interaction between the xanthines and both L-PIA and CDP. When combined with the caffeine training dose, pentobarbital also produced a dose-dependent decrease in response rate but not in drug lever choices. Finally, papaverine generalized to the caffeine cue in a dose-dependent fashion. In a second experiment, rats trained to discriminate CDP from saline showed no generalization in L-PIA tests. CDP-appropriate responding was not significantly affected when the CDP training dose was combined with caffeine. These data indicate that: (a) methylxanthine interactions with L-PIA and CDP on response rate likely involve blockade of adenosine mechanisms; (b) the xanthine cue does not appear to depend on interactions with adenosine receptors; and (c) the xanthine cue may involve effects on cyclic AMP activity and/or interaction with the BDZ/GABA receptor complex.
Holloway
F A
FA
Modrow
H E
HE
Michaelis
R C
RC
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002707:Chlordiazepoxide / Q000494:pharmacology; D003216:Conditioning, Operant; D003463:Cues; D004193:Discrimination Learning; D008297:Male; D010208:Papaverine / Q000494:pharmacology; D010424:Pentobarbital / Q000494:pharmacology; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011963:Receptors, GABA-A / Q000187:drug effects*; D011983:Receptors, Purinergic; D013806:Theophylline / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D002110:Caffeine; D002707:Chlordiazepoxide; D013806:Theophylline; D010208:Papaverine; D010424:Pentobarbital