Effects of naloxone on dopamine release in the nigrostriatal system

Simultaneously with a systemic injection of naloxone (NAL), the effects of the nigral application of the d(+)-amphetamine (AMPH) or of right forepaw stimulation on the release of [3H]dopamine [( 3H]DA) in the two caudate nuclei (CN) and the two substantia nigrae (SN) were examined in halothane-anesthetized cats. These experiments were carried out using four push-pull cannulae implanted bilaterally in the CN and SN and continuously supplied with [3H]tyrosine [( 3H]Tyr), the metabolic precursor of dopamine. Nigral AMPH application (1 muM) produced a local increase of the [3H]DA in spite of the NAL injection (5 mg/kg) but the presence of this drug prevented the expected effect of AMPH in the three other structures. Furthermore, the effects of electrical forepaw stimulation (EPS) were abolished by injection of NAL. NAL alone had no effect on the spontaneous release of [3H]DA. It is concluded that antagonism between NAL and AMPH could be due: (1) to enkephalinergic control of dopamine regulated nigral efferents, (2) to an action on the thalamic structures responsible for the reciprocal control of the two nigrostriatal dopaminergic pathways.