Dizocilpine (MK-801) and tetrodotoxin influence accumbal dopamine release evoked by intrapallidal morphine

It has been hypothesized that the intrapallidal morphine-induced dopamine release in the nucleus accumbens may be mediated by thalamocorticostriatal or mesolimbic pathways. In order to challenge the above hypothesis, we examined whether changes in accumbal dopamine and its metabolites produced by intrapallidal morphine a) are associated with local excitatory amino acid neurotransmission b) are determined by impulse propagation in dopamine neurons and c) are observed both ipsi- and contralateral to the morphine administration site. In vivo microdialysis was 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 microliters/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 (MK-801) into the nucleus accumbens or the sodium channel blocker tetrodotoxin into the medial forebrain bundle. Drugs' application was performed via reverse dialysis. Concentrations of dopamine, 3,4-dihydroxyphenyl acetic acid (DOPAC) and homovanillic acid (HVA) in the collected dialysate were measured by high performance liquid chromatography with electrochemical detection. Morphine administration resulted in elevated levels of dopamine in the ipsilateral and of DOPAC and HVA in both the ipsi- and contralateral nucleus accumbens. Dizocilpine (MK-801) (0.3 mM) did not influence the basal levels of dopamine, DOPAC or HVA in the nucleus accumbens. Ipsilaterally, dizocilpine (MK-801) inhibited the effect of morphine on dopamine release, whereas it increased significantly the effect of the drug on DOPAC and HVA. Tetrodotoxin (3 microM) reversed the effect of intrapallidal morphine on dopamine, DOPAC or HVA in the ipsilateral nucleus accumbens. The results show that the intrapallidal morphine-induced dopaminergic activation in the ipsilateral nucleus accumbens is dependent upon both phasic and tonic activation of dopaminergic neurons. They suggest that both the thalamocorticostriatal and the mesolimbic dopamine pathways may mediate the investigated effect of morphine.