Behavioral activity of some novel aporphines in rats with 6-hydroxydopamine lesions of caudate or nucleus accumbens.
The behavioral actions of some novel aporphines have been examined in rats with selective unilateral 6-hydroxydopamine (6OHDA)-induced destruction of nigrostriatal dopaminergic neurons, and in rats with bilateral 6OHDA-induced destruction of mesolimbic dopaminergic neurons. Dopaminomimetics such as apomorphine (APO) in these animal models elicit circling behavior and locomotor activity respectively. In animals with unilateral nigrostriatal lesions (-)-2,10,11-trihydroxy-N-n-propylnoraporphine (TNPA) and (-)-10,11-methylenedioxy-N-n-propylnoraporphine (MDO-NPA) elicited weak, but prolonged, contraversive circling, whereas (-)-2,10,11-trihydroxyaporphine (2-OH.APO) was inactive. In animals with bilateral destruction of mesolimbic dopaminergic neurons TNPA and MDO-NPA elicited a strong stimulation of locomotor activity, while 2-OH.APO was inactive. The results suggest that TNPA and MDO-NPA, but not 2-OH.APO, exert central dopaminomimetic effects in vivo. The results are also consistent with previous data indicating that N-propyl substitution of aporphines causes a relative enhancement of activity in animal models which emphasise effects at mesolimbic rather than striatal dopaminergic receptors.
D000818:Animals; D001060:Aporphines / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002421:Caudate Nucleus / Q000187:drug effects*; D003342:Corpus Striatum / Q000502:physiology; D004298:Dopamine / Q000378:metabolism; D006801:Humans; D006892:Hydroxydopamines / Q000494:pharmacology*; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009714:Nucleus Accumbens / Q000187:drug effects*; D016627:Oxidopamine; D051381:Rats; D011919:Rats, Inbred Strains; D012686:Septal Nuclei / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects; D013378:Substantia Nigra / Q000502:physiology; D013997:Time Factors
D001060:Aporphines; D006892:Hydroxydopamines; D016627:Oxidopamine; D004298:Dopamine