Discriminative stimulus effect of flesinoxan: effect of 5-HT1A antagonists and PCPA.
Rats were trained to discriminate 0.3 mg/kg (IP) flesinoxan from saline in a standard two-lever operant procedure and thereafter subjected to generalization and antagonism tests with the 5-HT1A receptor agonist ipsapirone and the beta-adrenergic/5-HT1 receptor antagonist pindolol. Ipsapirone (3.0 mg/kg) completely substituted for flesinoxan. Both the flesinoxan (0.3 mg/kg) and the ipsapirone cue (3.0 mg/kg) were dose-dependently blocked by (+/-)-pindolol. In a second group of rats, trained to discriminate 0.5 mg/kg (IP) of flesinoxan from saline, the putative 5-HT1A antagonist NAN-190 (in the dose range of 1.0 to 6.0 mg/kg) partially blocked the cue of flesinoxan. Generalization studies revealed that the flesinoxan cue could not be mimicked by NAN-190 (3.0 mg/kg). Finally, rats were pretreated with the 5-HT depletor parachlorophenylalanine (PCPA) and thereafter tested with the flesinoxan training dose (0.5 mg/kg). PCPA pretreatment did not significantly attenuate the recognition of the flesinoxan cue. The present results are in agreement with previous findings concerning the stimulus effect of flesinoxan and point to a mechanism that involves the activation of 5-HT1A receptors in the brain. Depletion of 5-HT did not significantly affect the stimulus effect of flesinoxan, suggesting that presynaptic 5-HT1A receptors do not play a crucial role in the mechanism underlying the stimulus effect of flesinoxan.
Department of Psychopharmacology, Faculty of Pharmacy, Utrecht University, The Netherlands.
C E
CE
Ybema
J L
JL
Slangen
B
B
Olivier
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D004193:Discrimination Learning / Q000187:drug effects* / Q000502:physiology; D010134:Fenclonine / Q000494:pharmacology*; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000494:pharmacology
D010879:Piperazines; D011743:Pyrimidines; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; C056895:flesinoxan; C043077:ipsapirone; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D010869:Pindolol; D010134:Fenclonine