alpha-Adrenergic modulation of hypothalamic self-stimulation: effects of phenoxybenzamine, yohimbine, dexamphetamine and their interactions with clonidine.
Eur J Pharmacol, 1978/12/15;53(1):1-8.
Hunt GE, Atrens DM, Becker FT, Paxinos G
PMID: 216557
Impact factor: 5.195
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; Dextroamphetamine; Drug Interactions; Electrodes, Implanted; Hypothalamus; Male; Methyltyrosines; Phenoxybenzamine; Rats; Receptors, Adrenergic; Receptors, Adrenergic, alpha; Self Stimulation; Yohimbine
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