Behavioural evidence that different neurochemical mechanisms underly stretching-yawning and penile erection induced in male rats by SND 919, a new selective D2 dopamine receptor agonist.
The behavioural effects induced in male Wistar rats by SND 919, a new drug reputed to have selective agonistic activity at D2 dopamine (DA) receptors, were studied. The following aspects of behaviour were considered: motor activity, stretching-yawning (SY), penile erection (PE) and stereotyped behaviour (SB). Intraperitoneal injection (IP) of the drug (0.01-20 mg/kg) induced an SY syndrome in the form of a bell-shaped dose-response curve, the effect being maximal at the dose of 0.1 mg/kg and disappearing completely at 10 mg/kg. SND 919 also potently elicited PE; this latter effect, however, was not coincident with SY induction, being maximal at 1 mg/kg and persisting at 10 and 20 mg/kg. SND 919-induced SY was potently antagonized by pretreatment not only with the D2 antagonist, L-sulpiride (20 mg/kg), but also with the alpha 2 antagonist, yohimbine (1, 3 mg/kg), and the more selective alpha 2 antagonist, idazoxan (1, 2 and 5 mg/kg). While sulpiride also decreased SND 919-induced PE, idazoxan at all doses and yohimbine at 1 mg/kg did not affect this behaviour. Inhibition of motor activity was induced by the D2 agonist at low doses (0.05, 0.1 mg/kg), while at high doses (1, 10 and 20 mg/kg), it was actually replaced by a form of SB characterized by downward sniffing and licking. When, for comparison, the D2 agonist, RU 24213 (0.1-20 mg/kg IP), was tested for PE, SY, motor activity and SB, it displayed a behavioural pattern very similar to that obtained with SND 919. Idazoxan (2 mg/kg), administered before RU 24213 (10 mg/kg), significantly antagonized the drug-induced SY, but not PE.(ABSTRACT TRUNCATED AT 250 WORDS)
Ferrari
F
F
Institute of Pharmacology, University of Modena, Italy.
Pelloni
F
F
Giuliani
D
D
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D052160:Benzothiazoles; D001923:Brain Chemistry / Q000187:drug effects*; D004146:Dioxanes / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology*; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D019329:Idazoxan; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010410:Penile Erection / Q000187:drug effects*; D010627:Phenethylamines / Q000494:pharmacology; D000077487:Pramipexole; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013239:Stereotyped Behavior / Q000187:drug effects; D013469:Sulpiride / Q000494:pharmacology; D013844:Thiazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015000:Yawning / Q000187:drug effects*; D015016:Yohimbine / Q000494:pharmacology
D000317:Adrenergic alpha-Antagonists; D052160:Benzothiazoles; D004146:Dioxanes; D018491:Dopamine Agonists; D065127:Dopamine D2 Receptor Antagonists; D010627:Phenethylamines; D017448:Receptors, Dopamine D2; D013844:Thiazoles; D015016:Yohimbine; C016868:N-n-propyl-N-phenylethyl-4(3-hydroxyphenyl)ethylamine hydrochloride; D013469:Sulpiride; D000077487:Pramipexole; D019329:Idazoxan