title: Tetrahydropapaveroline injected in the ventral tegmental area shifts dopamine efflux differentially in the shell and core of nucleus accumbens in high-ethanol-preferring (HEP) rats.
abstract: 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.
authors.affiliation: Department of Pharmacology and Center for Alcohol and Drug Abuse Studies, School of Medicine, East Carolina University, Greenville, NC 27858, USA.
authors.forename: R D
authors.initials: RD
authors.lastname: Myers
authors.forename: D E
authors.initials: DE
authors.lastname: Robinson
mesh_terms: D000437:Alcoholism / Q000209:etiology / Q000378:metabolism; D000818:Animals; D004298:Dopamine / Q000378:metabolism*; D005260:Female; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D013765:Tetrahydropapaveroline / Q000494:pharmacology*; D017557:Ventral Tegmental Area / Q000187:drug effects*
chemical_list: D013765:Tetrahydropapaveroline; D004298:Dopamine