Effects on locomotor activity after local application of (+)-UH232 in discrete areas of the rat brain.
The preferential dopamine autoreceptor, and slightly D3 preferring, antagonist (+)-UH232 (cis-(+)-(1S,2R)-5-methoxy-1-methyl-2-(n-dipropylamino) tetralin) increases locomotor activity and synaptic dopamine release in the nucleus accumbens and striatum after systemic administration to the rat. As shown in this study, (+)-UH232, was unable to produce an increase in locomotor activity measured for 60 minutes after local administration into the terminal or somato-dendritic regions of the mesolimbic dopamine pathways or into the lateral ventricle. Instead, a dose dependent decrease of spontaneous locomotor activity after local application (0.05-50.0 nmol/side) of (+)-UH232 into the nucleus accumbens, was seen. A similar reduction in locomotor activity was produced by the classical dopamine antagonist raclopride. Analysis of the dose*time interactions on locomotor activity did, however, indicate that there is a significant dose*time interaction after local application of (+)-UH232 into the lateral ventricle and VTA. Raclopride, on the other hand, produced only a weak time dependent effect in the VTA. The potential problem of Leao's spreading depression in micro-injection experiments were considered, however, spreading depression does not seem to influence the effects of (+)-UH232 locally applied into the nucleus accumbens. In conclusion, both (+)-UH232 and raclopride produced a dose dependent decrease in spontaneous locomotor activity when examined as the total activity count over 60 minutes after local application into the N Acc.
Kling-Petersen
T
T
Department of Pharmacology, University of Göteborg, Sweden.
Ljung
E
E
Waters
N
N
Svensson
K
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D013181:Cortical Spreading Depression / Q000187:drug effects; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006185:Habituation, Psychophysiologic; D007276:Injections, Intraventricular; D008297:Male; D008845:Microinjections; D009043:Motor Activity / Q000187:drug effects*; D009714:Nucleus Accumbens; D020891:Raclopride; D051381:Rats; D017207:Rats, Sprague-Dawley; D012457:Salicylamides / Q000494:pharmacology; D017557:Ventral Tegmental Area
D018492:Dopamine Antagonists; D012457:Salicylamides; D020891:Raclopride; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C045971:UH 232