alpha-Adrenergic modulation of hypothalamic self-stimulation: effects of phenoxybenzamine, yohimbine, dexamphetamine and their interactions with clonidine

Eur J Pharmacol. 1978 Dec 15;53(1):1-8. doi: 10.1016/0014-2999(78)90261-3.

Abstract

The alpha-adrenoceptor agonist clonidine (12.5--50.0 microgram/kg) produced a dose-dependent increase in the latency to initiate lateral hypothalamic stimulation. The insurmountable postsynaptic alpha-adrenoceptor antagonist phenoxybenzamine (0.2-0.8 mg/kg) had no effect on self-stimulation by itself, but potentiated the inhibitory effects of clonidine. The fact that the concurrent escape behavior to the intracranial stimulation was unchanged by either clonidine or the phenoxybenzamine-clonidine combination suggests that the inhibition is specific to the rewarding component of hypothalamic stimulation. Yohimbine (0.5--2.0 mg/kg) produced a dose-dependent increase in both response latencies. This lack of behavioral specificity may reflect yohimbine's wide range of pharmacological activity, Dexamphetamine (0.25--0.50 mg/kg) reversed clonidine's inhibition of self-stimulation reward in a specific and dose-dependent fashion. This reversal could be blocked by previous inhibition of catecholamine synthesis with alpha-methyl-p-tyrosine. These data support the concept that the alpha-adrenoceptors play a critical role in the modulation of hypothalamic self-stimulation reward. They further suggest that the inhibitory effects of clonidine on self-stimulation reward represent an agonist effect on presynaptic alpha-adrenoceptors.

MeSH terms

  • Animals
  • Clonidine / pharmacology*
  • Dextroamphetamine / pharmacology
  • Drug Interactions
  • Electrodes, Implanted
  • Hypothalamus / physiology*
  • Male
  • Methyltyrosines / pharmacology
  • Phenoxybenzamine / pharmacology
  • Rats
  • Receptors, Adrenergic / drug effects*
  • Receptors, Adrenergic, alpha / drug effects*
  • Receptors, Adrenergic, alpha / physiology
  • Self Stimulation / drug effects*
  • Yohimbine / pharmacology

Substances

  • Methyltyrosines
  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha
  • Phenoxybenzamine
  • Yohimbine
  • Clonidine
  • Dextroamphetamine