Since the 1970s
tetrahydropapaveroline (THP) and other
tetrahydroisoquinoline alkaloids have been implicated in the etiology of
alcoholism. When injected into the cerebral ventricle or at specific sites in the mesolimbic system such as the ventral tegmental area (VTA), THP evokes spontaneous and intense intake of alcohol in the nondrinking animal. Further, THP evokes the extracellular efflux of
dopamine in the nucleus accumbens (NAC), which comprises, in part, the postulated alcohol drinking "circuit" of neurons. The purpose of this study was to characterize the action of a THP reactive structure, the VTA, on the activity of
dopamine and its metabolism in the NAC. In the anesthetized high-
ethanol-preferring (HEP) rat, artificial CSF was perfused for 10 min at a rate of 10 microl per min specifically in either the core or shell of the NAC. A microbore push-pull
cannula system was selected over a microdialysis probe because of its superior recovery of
neurotransmitters and tip exposure of less than 1.0 mm. After a series of 5-min perfusions, a single microinjection of 5.0 microg/microl of THP was made in the ipsilateral VTA while the NAC was perfused simultaneously. Sequential samples of the NAC perfusate were assayed by an HPLC coulometric system to quantitate the concentrations of
dopamine and its metabolites,
DOPAC and HVA, as well as the
5-HT metabolite,
5-HIAA. The results showed that THP injected in the VTA caused a significant increase by 94 +/- 23% in the efflux of
dopamine from the core of the NAC. Conversely, the THP injected identically in the VTA suppressed the efflux of
dopamine within the shell of the NAC by 51 +/- 10%. The levels of
DOPAC, HVA and
5-HIAA within the core and shell of the NAC generally paralleled the increase and decrease in efflux, respectively, of
dopamine. CSF control
injections in the VTA as well as
injections outside of the VTA failed to alter
dopamine or metabolite activity in the NAC. These results demonstrate that the presence of THP in the VTA alters directly the function of the pathway of mesolimbic neurons generally and the dopaminergic system specifically. That such a perturbation could account for the induction of alcohol preference is proposed in relation to a reinforcing mechanism involving opioidergic and dopaminergic elements.