Abstract：
:Rats with unilateral 6-hydroxydopamine lesions of the substantia nigra became briefly sedated and hypothermic after the acute injection of nicotine s.c. (0.4 or 0.8 mg/kg free base). When nicotine was repeated 5 days per week there was rapid tolerance for the sedation and slower tolerance for the hypothermia and the lesioned animals began to rotate ipsiversively after each injection. Stereotypic behavior was also noted. Rats injected with nicotine 5 days per week and nigrally lesioned on the 24th day rotated promptly on their first postoperative injection of nicotine. The nicotinic antagonist, mecamylamine (1.0 mg/kg i.p.), completely blocked the induced rotation. The appearance of rotation did not seem to depend on tolerance to sedation. The direction of rotation indicated enhancement of activity in the intact nigrostriatal system. However, 10 min after the acute injection of 0.8 mg/kg nicotine no change was found in the ratios of dopamine to its metabolites DOPAC and homovanillic acid in the substantia nigra, caudate-putamen, nucleus accumbens, olfactory tubercle, frontal cortex, or ventral tegmental area. Rats given 0.4 or 0.8 mg/kg nicotine 5 days per week and either lesioned prior to nicotine or lesioned during the third week rotated during the sixth week without any sign of tolerance. One day after the 30th injection in intact or lesioned rats the ratios of dopamine to its metabolites did not differ from those in saline controls on either the right or left side of any of the regions examined. There was no evidence of a change in dopamine metabolism after an acute challenge with nicotine or of a sustained change after repeated injection. The possibility remains that repeated nicotine modifies the dopaminergic response to nicotine without causing a sustained change in metabolism.
journal_name
Brain Resjournal_title
Brain researchauthors
Lapin EP,Maker HS,Sershen H,Hurd Y,Lajtha Adoi
10.1016/0006-8993(87)91114-0subject
Has Abstractpub_date
1987-03-31 00:00:00pages
351-63issue
2eissn
0006-8993issn
1872-6240pii
0006-8993(87)91114-0journal_volume
407pub_type
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