Antagonism of the stimulus effects of yohimbine and 8-hydroxydipropylaminotetralin

Pharmacol Biochem Behav. 1993 Apr;44(4):851-5. doi: 10.1016/0091-3057(93)90016-m.

Abstract

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 8-Hydroxy-2-(di-n-propylamino)tetralin / antagonists & inhibitors*
  • 8-Hydroxy-2-(di-n-propylamino)tetralin / pharmacology
  • Alprenolol / pharmacology
  • Animals
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Discrimination, Psychological / drug effects*
  • Hippocampus / drug effects
  • Hippocampus / metabolism
  • Male
  • Pindolol / pharmacology
  • Piperazines / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Inbred F344
  • Receptors, Adrenergic, alpha / drug effects
  • Receptors, Adrenergic, alpha / metabolism
  • Serotonin / physiology
  • Serotonin Antagonists / pharmacology
  • Yohimbine / antagonists & inhibitors*
  • Yohimbine / pharmacology

Substances

  • Piperazines
  • Receptors, Adrenergic, alpha
  • Serotonin Antagonists
  • 1-(2-methoxyphenyl)-4-(4-(2-phthalimido)butyl)piperazine
  • Yohimbine
  • Serotonin
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Alprenolol
  • Pindolol