Effects of single and repeated treatment with antidepressants on apomorphine-induced yawning in the rat: the implication of alpha-1 adrenergic mechanisms in the D-2 receptor function.
Acute (10 or 20 mg/kg IP) and subchronic (2 x 5 or 10 mg/kg IP daily for 7 days) effects of desipramine, imipramine, maprotiline, (+)- and (-)-oxaprotiline enantiomers as well as selective 5-HT-uptake inhibitors citalopram and ifoxetine on yawning, induced by low doses of apomorphine, were investigated in the rat. In addition, the effects of alpha-1 receptor agonist adrafinil and antagonist prazosin were also tested. After acute treatment, desipramine, the stereoselective NA-uptake inhibiting (+)-enantiomer of oxaprotiline, and the alpha-1 agonist adrafinil, markedly and significantly suppressed yawning. Prazosin, in contrast, clearly potentiated it. This potentiating effect was abolished by the pretreatment with (+)-oxaprotiline and adrafinil. Other drugs were inactive. After subchronic administration, yawning was antagonized by NA-uptake-inhibiting antidepressants, including imipramine and maprotiline. By comparison to the acute treatment, the inhibitory effects of desipramine and (+)-oxaprotiline were considerably enhanced. Neither selective 5-HT-uptake inhibitors nor (-)-oxaprotiline (levoprotiline) were active. Antidepressants therefore modulate the functional activity of D-2 receptors, activated by low doses of apomorphine, predominantly by the virtue of their noradrenergic enhancing properties. This modulatory effect appears to be mediated by alpha-1 adrenergic receptors.
Delini-Stula
A
A
Research Laboratories, CIBA-GEIGY Ltd., Basle, Switzerland.
Hunn
C
C
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001058:Apomorphine / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004347:Drug Interactions; D006877:Hydroxamic Acids / Q000494:pharmacology; D008297:Male; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D011954:Receptors, Dopamine / Q000187:drug effects*; D015000:Yawning / Q000187:drug effects*
D000316:Adrenergic alpha-Agonists; D000928:Antidepressive Agents; D006877:Hydroxamic Acids; D011942:Receptors, Adrenergic, alpha; D011954:Receptors, Dopamine; C022116:adrafinil; D001058:Apomorphine; D011224:Prazosin