title: Local and distal effects induced by unilateral striatal application of opiates in the absence or in the presence of naloxone on the release of dopamine in both caudate nuclei and substantiae nigrae of the cat.
abstract: Halothane-anesthetized cats implanted with push-pull cannulae in both caudate nuclei (CN) and substantiae nigrae (SN) were used to study the effects of naloxone and various opiates when applied into the left CN on the release of newly synthetized tritiated dopamine (DA) from nerve terminals and dendrites of the two nigro-striatal dopaminergic pathways. In all cases, the drugs (naloxone, opiates alone or in the presence of naloxone) were applied for 30 min into the left CN. When applied alone, naloxone (10(-6) M) induced a delayed reduction in tritiated DA release both in the ipsilateral and contralateral CN. These effects were seen after removal of the drug from the superfusion fluid. Complementary experiments made with tritiated naloxone (10(-6) M) revealed that the contralateral effect on DA release was not due to a diffusion of the opiate antagonist from its application site. Locally, D-Ala2, Met-enkephalinamide (D-Ala2, Met-Enk, 10(-6) M) and the potent delta agonist Tyr-D-Ser-Gly-Phe-Leu-Thr (DSThr, 5 X 10(-8) M) induced a biphasic increase in tritiated DA release. The local changes in tritiated DA release evoked by morphine (10(-6) M) and mu agonists such as Tyr-D-Ala-Gly-NH-C6H13 (10(-8) M) and fentanyl (10(-8) M) differed from those of delta agonists and furthermore differed from each other. For instance, morphine induced a delayed increase in tritiated DA release whereas a biphasic increase followed by a delayed inhibition occurred with fentanyl. Among all the opiates tested D-Ala2-Met-Enk was the only one which elicited a distal effect, that is a reduction of tritiated DA release in the ipsilateral SN. Marked differences in these opiates' effects on tritiated DA release occurred both locally and in distal structures when opiates were applied simultaneously with naloxone (10(-6) M). Locally, the changes induced by mu agonists were particularly altered since during morphine's application with naloxone a reduction of tritiated DA release occurred. In addition, the opiate antagonist prevented the second increase and the delayed inhibition of tritiated DA release evoked by fentanyl (10(-8) M). Interestingly, the combined application of naloxone with either D-Ala2, Met-Enk (10(-6) M), DSThr (5 X 10(-8) M) or morphine (10(-6) M) resulted in the appearance of changes in tritiated DA release in contralateral structures. The most striking effect was seen with D-Ala2, Met-Enk which enhanced tritiated DA release in the contralateral CN and SN. These results are discussed in the light of the involvement of several types of opiate receptors and of the polysynaptic pathways responsible for the distal changes in dopaminergic transmission.
mesh_terms: D000818:Animals; D002415:Cats; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000502:physiology*; D004298:Dopamine / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives / Q000494:pharmacology; D005260:Female; D005283:Fentanyl / Q000494:pharmacology; D007839:Functional Laterality; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism*
chemical_list: D009294:Narcotics; D009270:Naloxone; D004744:Enkephalin, Methionine; C022118:enkephalinamide-Met, Ala(2)-; D009020:Morphine; D005283:Fentanyl; D004298:Dopamine