Alpha 1- and alpha 2-adrenoreceptor antagonists differentially influence locomotor and stereotyped behaviour induced by d-amphetamine and apomorphine in the rat.
The importance of dopamine (DA) in mediating locomotor, exploratory and stereotyped behaviour in rodents is well established. Evidence also indicates a modulatory role for noradrenaline (NA) although, due to nonspecificity. of previously available agents, a precise role remains undefined. The effects of the specific and selective alpha-adrenoreceptor antagonists idazoxan (alpha 2) and prazosin (alpha 1) on behaviour induced by amphetamine and apomorphine have been investigated in the rat. d-Amphetamine (2 mg/kg) induced hyperactive locomotion and exploration. Pretreatment with prazosin (1 mg/kg) markedly reduced these responses. In contrast, pretreatment with idazoxan (20 mg/kg) only marginally altered d-amphetamine hyperactivity. Apomorphine (0.5 mg/kg) induced biphasic locomotor and exploratory activity. Neither alpha-antagonist affected the initial burst of activity (60 min), although prazosin inhibited whereas idazoxan potentiated the secondary phase (90-180 min). At higher dosage, amphetamine (6 mg/kg) and apomorphine (2 mg/kg) induced stereotyped behaviours. Prazosin pretreatment enhanced stereotyped gnawing and decreased sniffing and locomotion, whereas idazoxan increased locomotion and decreased amphetamine-induced mouth movements. These data indicate that DA-induced locomotor and stereotyped behaviours are differentially influenced (in opposite directions) by both alpha1- and alpha 2-adrenoreceptor antagonists. NA may thus modulate the expression and character of behaviour by influencing DA function in certain brain areas.
Dickinson
S L
SL
Department of Pharmacology, Reckitt & Colman plc, Kingston-Upon-Hull, North Humberside, UK.
Gadie
B
B
Tulloch
I F
IF
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D003913:Dextroamphetamine / Q000494:pharmacology*; D004146:Dioxanes / Q000494:pharmacology; D019329:Idazoxan; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013239:Stereotyped Behavior / Q000187:drug effects*; D013997:Time Factors
D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D001058:Apomorphine; D003913:Dextroamphetamine; D011224:Prazosin; D019329:Idazoxan