Depletion of central catecholamines alters amphetamine- and fenfluramine-induced taste aversions in the rat.
Conditioned taste aversions induced by pairing the consumption of saccharin with an amphetamine injection are attenuated in rats with depletion of central catecholamines caused by intraventricular administration of 6-hydroxydopamine (6-OHDA). The hypothesis that dopamine (DA) depletion is responsible for this effect was tested. The reduction in conditioning caused by intraventricular 6-OHDA could not be duplicated either with injections of 6-OHDA into the substantia nigra (Experiment 1) or with intraventricular 6-OHDA injections in animals pretreated with desmethylimipramine (Experiment 2). Both treatments, however, produced large depletions of telencephalic DA. 6-Hydroxydopa infusions caused a preferential loss of telencephalic norepinephrine (NE) but also failed to alter taste aversion learning. It is concluded that the effect of intraventricular 6-OHDA on amphetamine-induced aversions was the result of depletion of both NE and DA. In a third experiment the generality of the effect was examined by pairing saccharin consumption with injections of the amphetamine congener fenfluramine. Depletion of both NE and DA failed to alter fenfluramine-induced aversions. Infusion of 6-OHDA into the substantia nigra, however, retarded the extinction of such an aversion. Evidence is discussed for a peripheral site of action for fenfluramine in the conditioned aversion paradigm.
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects* / Q000502:physiology; D003891:Desipramine / Q000494:pharmacology; D003913:Dextroamphetamine / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D004326:Drinking / Q000187:drug effects; D005277:Fenfluramine / Q000494:pharmacology*; D006892:Hydroxydopamines / Q000494:pharmacology; D007276:Injections, Intraventricular; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D051381:Rats; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism; D013649:Taste / Q000187:drug effects* / Q000502:physiology; D013687:Telencephalon / Q000187:drug effects / Q000378:metabolism*
D006892:Hydroxydopamines; D005277:Fenfluramine; D003891:Desipramine; D003913:Dextroamphetamine; D004298:Dopamine; D009638:Norepinephrine