Monoaminergic mechanisms of stimulation-produced analgesia
1975; Elsevier BV; Volume: 94; Issue: 2 Linguagem: Inglês
10.1016/0006-8993(75)90062-1
ISSN1872-6240
AutoresHuda Akil, John C. Liebeskind,
Tópico(s)Neuroscience and Neural Engineering
ResumoThe roles played by the cerebral monoamines (dopamine, noradrenaline and serotonin) in stimulation-produced analgesia (SPA) have been investigated in the rat employing the tail flick test. SPA was elicited through bipolar electrodes chronically implanted in the mesencephalic periaqueductal gray matter, an area previously shown to yield potent and reliable analgesic effects. Four approaches were used to alter transmission in monoamine pathways. Depletion of monoamines by administration of tetrabenazine (TBZ),p-chlorophenylalanine (PCPA), alpha-methyl-para-tyrosine (AMPT), or disulfiram. Replacement of depleted monoamine stores by appropriate precursors (5-HTP orl-DOPA) in combination with a peripheral decar☐ylase inhibitor. Potentiation of monoamine systems by administration of precursors to previously untreated animals or by administration of a dopamine receptor stimulator, apomorphine. Blockade of catecholamine receptors by haloperidol or of opamine receptors by pimozide. These 4 approaches yielded internally consistent results. Depletion of all 3 monoamines (TBZ) led to a powerful inhibition of SPA. Original levels of SPA were restored by injection of either 5-HTP orl-DOPA. Specific depletion of serotonin (PCPA) caused a reduction in SPA, whereas elevation of serotonin levels (5-HTP) caused an increase in SPA. Dopamine receptor blockade (pimozide) decreased SPA, whereas the precursor (l-DOPA) and a dopamine receptor stimulator (apomorphine) increased SPA. On the other hand, selective depletion of noradrenaline (disulfiram) caused anincrease in SPA; and, at a time when noradrenaline levels are depressed and dopamine levels are elevated (AMPT +l-DOPA), SPA was seen to be particularly enhanced.
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