The modified Geller-Seifter test in rats was insensitive to GABAB receptor positive modulation or blockade, or 5-HT1A receptor activation.
BACKGROUND
Both the GABA(B) receptor positive modulator GS39783 and the GABA(B) receptor antagonist CGP46381 exhibit anxiolytic-like properties in animal models. In the present studies, the effects of GS39783 and CGP46381 in the modified Geller-Seifter task were assessed. First, the predictive validity of the task was confirmed by assessing the effects of multiple anxiolytic and non-anxiolytic compounds on punished and unpunished responding.


METHODS
Rats were trained in the modified Geller-Seifter task. After successful acquisition of the task, chlordiazepoxide, diazepam, MPEP, haloperidol, GS39783, 8-OH-DPAT, alprazolam and CGP46381 were tested consecutively. For each test compound, doses were administered in a randomized, counter-balanced, within-subjects design. Drug tests were performed only when rats exhibited baseline performance (the punished and time-out response rates were less than 10% of the unpunished response rate).


RESULTS
Chlordiazepoxide, diazepam, alprazolam and MPEP released punished responding with variable effects on unpunished responding. Haloperidol had a small but significant effect on punished responding at an intermediate dose, and decreased unpunished responding at the highest dose tested. In contrast, administration of the GABA(B) receptor positive modulator GS398783 or the GABA(B) receptor antagonist CGP46381 at doses up to 30 mg/kg had no effects on either punished or unpunished responding. The 5-HT(1A) agonist 8-OH-DPAT did not release punished responding, but significantly decreased unpunished responding at the highest dose tested.


CONCLUSIONS
The modified Geller-Seifter task generally exhibits good predictive validity for anxiolytic-like compounds. Neither GABA(B) receptor positive allosteric modulation nor blockade exhibited anxiolytic-like properties in the modified Geller-Seifter task. The 5-HT(1A) partial agonist buspirone was similarly ineffective.
Paterson
Neil E
NE
Pharmacology, PsychoGenics, Inc., 765 Old Saw Mill River Rd., Tarrytown, NY 10591, USA.
Hanania
Taleen
T
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001007:Anxiety / Q000175:diagnosis* / Q000188:drug therapy; D001522:Behavior, Animal / Q000187:drug effects; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D003220:Conflict, Psychological; D004195:Disease Models, Animal; D018492:Dopamine Antagonists / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004597:Electroshock / Q000379:methods; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018682:GABA Agents / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D011963:Receptors, GABA-A / Q000502:physiology*; D012055:Reinforcement Schedule; D015203:Reproducibility of Results; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D018492:Dopamine Antagonists; D018691:Excitatory Amino Acid Antagonists; D018682:GABA Agents; D011725:Pyridines; D011963:Receptors, GABA-A; D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C121465:6-methyl-2-(phenylethynyl)pyridine; D006220:Haloperidol