Nicotine acts in CNS, but the pathways and mechanisms of its actions are poorly understood. Recent studies suggest an interaction between brain
nicotinic receptors and endogenous
opioid peptides. Acute administration of
nicotine may alter
enkephalin release without affecting brain
enkephalin level.
Tyr-Gly-Gly has been shown previously to be an extraneuronal metabolite of
opioid peptides derived from
proenkephalin A. Concentrations of
Tyr-Gly-Gly in brain were used to provide an index of
enkephalin release in vivo. Thus we examined the thesis that
nicotine alters brain neuronal
enkephalin release, by measuring
Tyr-Gly-Gly levels in specific brain nuclei from rats treated with
nicotine 0.3 mg/kg SC 10 min before
decapitation. Of 30 brain regions investigated, acute
nicotine increased
Tyr-Gly-Gly immunoreactivity in nucleus accumbens and in lower brain stem areas including dorsal raphe, pontine reticular formation, gigantocellular reticular formation, locus coeruleus, sensory trigeminal nucleus and the caudal part of ventrolateral medulla oblongata. Concomitantly,
nicotine produced a significant decrease in native
Met-enkephalin in central amygdala, flocculo-nodular lobe of cerebellum, caudal part of the ventrolateral medulla and intermediolateral cell column of the spinal cord. It is probable that the effects of
nicotine to increase
Tyr-Gly-Gly and alter
Met-enkephalin concentration are mediated by
nicotine-induced release of
enkephalin at these brain sites. Furthermore, some of the physiologic and pharmacologic effects of
nicotine may be mediated by such
enkephalin release.