Antagonism of the stimulus effects of yohimbine and 8-hydroxydipropylaminotetralin.
Stimulus control was established in rats using either 8-hydroxy-2-[di-n-propylamino]tetralin (DPAT) (0.2 mg/kg) or yohimbine (3 mg/kg). Tests were then conducted with purported antagonists at 5-hydroxytryptamine1A (5-HT1A) receptors. Drugs studied were NAN-190, [+/-]-pindolol, and [-]-alprenolol. In addition, each drug was characterized in terms of its affinity for 5-HT1A and alpha 2-adrenoceptors by means of radioligand binding techniques. None of the antagonists tested provided complete blockade of the stimulus effects of either DPAT or yohimbine. However, [+/-]-pindolol produced a statistically significant intermediate degree of antagonism of both DPAT and yohimbine. The affinities of DPAT, yohimbine, and NAN-190 for the 5-HT1A and alpha 2-adrenergic receptors, respectively, were sufficiently high to lead to some ambiguity of interpretation of the behavioral data. However, the results with [+/-]-pindolol, which has high affinity for the 5-HT1A receptor (34 nM) and negligible affinity for the alpha 2-adrenoceptor (24,600 nM), indicate that a significant component of yohimbine-induced stimulus control is mediated by the 5-HT1A receptor.
Department of Pharmacology and Therapeutics, School of Medicine and Biomedical Sciences, State University of New York, Buffalo 14214.
J C
JC
Winter
R A
RA
Rabin
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D000526:Alprenolol / Q000494:pharmacology; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D004192:Discrimination, Psychological / Q000187:drug effects*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010869:Pindolol / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011916:Rats, Inbred F344; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology; D015016:Yohimbine / Q000037:antagonists & inhibitors* / Q000494:pharmacology
D010879:Piperazines; D011942:Receptors, Adrenergic, alpha; D012702:Serotonin Antagonists; C058895:1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine; D015016:Yohimbine; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000526:Alprenolol; D010869:Pindolol