Chronic nicotine treatment counteracts the disappearance of tyrosine-hydroxylase-immunoreactive nerve cell bodies, dendrites and terminals in the mesostriatal dopamine system of the male rat after partial hemitransection.
Male Sprague-Dawley rats were partially hemitransected at the mesodiencephalic junction and treated with nicotine (nicotine hydrogen (+)-tartrate) using Alzet minipumps implanted subcutaneously. Nicotine was delivered for 2 weeks in a dose of 0.125 mg/kg/h resulting in a serum nicotine level of 50.0 +/- 5.1 ng/ml. Three other groups of rats were analyzed: hemitransected rats receiving saline treatment and sham-operated animals receiving nicotine and saline, respectively. The effects of hemitransection and nicotine rostrally as well as caudally to the lesion were evaluated with image analysis of tyrosine hydroxylase (TH)-immunoreactive (IR) nerve cell body and dendrite profiles in the rostral and caudal substantia nigra and of TH-IR nerve terminal profiles in the striatum. Adjacent sections were taken to Nissl staining. [3H]Nicotine binding in the midbrain and forebrain was studied by means of receptor autoradiography on partially hemitransected rats receiving no treatment. Catecholamine (CA) levels in the frontal cortex were measured using high-performance liquid chromatography (HPLC). Striatal dopamine (DA) function was analyzed studying apomorphine-induced (1.0 mg/kg) ipsilateral rotational behavior. The spontaneous behavior of the rats was evaluated with a hole board. Furthermore, body temperature and body weight were measured. The results demonstrated a lesion-induced disappearance of TH-IR cell body and dendrite profiles in the substantia nigra and of TH-IR nerve terminal profiles in the striatum. Similar findings were seen after Nissl staining. A significant counteraction of this disappearance was found in the nicotine-treated animals. On the lesioned animals a marked reduction of [3H]nicotine binding in the striatum and the substantia nigra was found. In the functional experiments an enhancement of the apomorphine-induced ipsilateral rotational behavior was demonstrated. The degree of rotation was positively correlated with the serum nicotine level. The study on spontaneous activity in the hole board showed a slower restoration of total activity in the hemitransected nicotine-treated rats. All these results are compatible with the hypothesis that the protective action of nicotine on the mesostriatal DA system may be due to a desensitization of excitatory nicotine cholinoceptors located on the nigral DA nerve cells, leading to a reduction of firing rate and reduced energy demands. Such an action of nicotine could be of importance for a possible anti-parkinsonian effect.
D000818:Animals; D002452:Cell Count; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology; D004298:Dopamine / Q000378:metabolism / Q000502:physiology*; D007839:Functional Laterality; D008297:Male; D009410:Nerve Degeneration / Q000187:drug effects*; D009411:Nerve Endings / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism / Q000502:physiology
D009538:Nicotine; D014446:Tyrosine 3-Monooxygenase; D004298:Dopamine