Abstract:
RATIONALE:Nicotine displays rewarding and aversive effects, and while dopamine has been linked with nicotine's reward, the neurotransmitter(s) involved with aversion remains speculative. The kappa-dynorphinergic system has been associated with negative motivational and affective states, and whether dynorphin (Dyn) contributes to the behavioral pharmacology of nicotine is a pertinent question. OBJECTIVE:We determined whether administration of a single dose of nicotine alters the biosynthesis of Dyn in the striatum of mice. RESULTS:Nicotine free base, 1 mg/kg, sc, induced a biphasic, protracted increase of striatal Dyn, an initial rise by 1 h, which declined to control levels by 2 h, and a subsequent increase, between 6 and 12 h, lasting over 24 h. At 1 h, the nicotine effect was dose dependent, with doses>or=0.5 mg/kg inducing a response. Prodynorphin mRNA increased by 30 min for over 24 h, and in situ hybridization demonstrated elevated signal in caudate/putamen and nucleus accumbens. The nicotinic antagonist mecamylamine prevented the Dyn response, and a similar effect was observed with D1- and D2-like dopamine receptor antagonists, SCH 23390, sulpiride, and haloperidol. The glutamate NMDA receptor antagonist MK-801 reversed the nicotine-induced increase of Dyn, while the AMPA antagonist NBQX had a marginal effect. CONCLUSIONS:We interpret our findings to indicate that acute nicotine enhances the synthesis and release of striatal Dyn. We propose that nicotine influences Dyn primarily through dopamine release and that glutamate plays a modulatory role. A heightened dynorphinergic tone may contribute to the aversive effects of nicotine in naive animals and first-time tobacco smokers.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Isola R,Zhang H,Tejwani GA,Neff NH,Hadjiconstantinou Mdoi
10.1007/s00213-008-1315-4subject
Has Abstractpub_date
2009-01-01 00:00:00pages
507-16issue
4eissn
0033-3158issn
1432-2072journal_volume
201pub_type
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更新日期:2010-04-01 00:00:00
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更新日期:1977-08-31 00:00:00
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更新日期:1980-01-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2005-02-01 00:00:00
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pub_type: 临床试验,杂志文章,随机对照试验
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更新日期:2013-12-01 00:00:00
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更新日期:2018-04-01 00:00:00
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pub_type: 杂志文章
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更新日期:2012-08-01 00:00:00
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更新日期:1979-04-11 00:00:00