DIZOCILPINE (MK-801) AND TETRODOTOXIN INFLUENCE ACCUMBAL DOPAMINE RELEASE EVOKED BY INTRAPALLIDAL MORPHINE

It has been hypothesized that the intrapallidal morphine-induced dopam ine release in the nucleus accumbens may be mediated by thalamocortico striatal or mesolimbic pathways. In order to challenge the above hypot hesis, we examined whether changes in accumbal dopamine and its metabo lites produced by intrapallidal morphine a) are associated with local excitatory amino acid neurotransmission b) are determined by impulse p ropagation in dopamine neurons and c) are observed both ipsi-and contr alateral to the morphine administration site. In vivo microdialysis wa s used to assess dopamine release and metabolism in the right and the left nucleus accumbens separately of awake, unrestrained rats. Vehicle or morphine hydrochloride (10 mu l/26.0 mM) was applied unilaterally into the pallidum alone or in combination with ipsilateral application of the N-methyl-D-aspartate (NMDA) receptor antagonist dizocilpine (M K-801) into the nucleus accumbens or the sodium channel blocker tetrod otoxin into the medial forebrain bundle. Drugs' application was perfor med via reverse dialysis. Concentrations of dopamine, 3,4-dihydroxyphe nyl acetic acid (DOPAC) and homovanillic acid (HVA) in the collected d ialysate were measured by high performance liquid chromatography with electrochemical detection. Morphine administration resulted in elevate d levels of dopamine in the ipsilateral and of DOPAC and HVA in both t he ipsi-and contralateral nucleus accumbens. Dizocilpine (MK-801) (0.3 mM) did not influence the basal levels of dopamine, DOPAC or HVA in t he nucleus accumbens. Ipsilaterally, dizocilpine (MK-801) inhibited th e effect of morphine on dopamine release, whereas it increased signifi cantly the effect of the drug on DOPAC and HVA. Tetrodotoxin (3 mu M) reversed the effect of intrapallidal morphine on dopamine, DOPAC or HV A in the ipsilateral nucleus accumbens. The results show that the intr apallidal morphine-induced dopaminergic activation in the ipsilateral nucleus accumbens is dependent upon both phasic and tonic activation o f dopaminergic neurons. They suggest that both the thalamocorticostria tal and the mesolimbic dopamine pathways may mediate the investigated effect of morphine. (C) 1998 Elsevier Science B.V./ECNP.