伪3尾4 nicotinic acetylcholine receptors in the medial habenula modulate the mesolimbic dopaminergic response to acute nicotine in聽vivo
- 作者：Sarah E. McCallum ; mccalls@mail.amc.edu ; Matthew A. Cowe ; Samuel W. Lewis ; Stanley D. Glick glicks@mail.amc.edu
- 关键词：Nicotine ; Dopamine ; Microdialysis ; 18-Methoxycoronaridine ; Nicotinic receptor ; Rat ; Medial habenula
- 刊名：Neuropharmacology
- 出版年：2012
- 期刊代码：33_00283908
- 类别：pha
- 出版时间：September, 2012
- 卷：63
- 期：3
- 页码：434-440
- 文件大小：754 K
摘要
Habenulo-interpeduncular nicotinic receptors, particularly those containing 伪3, 尾4 and 伪5 subunits, have recently been implicated in the reinforcing effects of nicotine. Our laboratory has shown that injection of 伪3尾4 nicotinic receptor antagonists into the medial habenula (MHb) decreases self-administration of multiple abused drugs, including nicotine (, ; ). However, it is unclear whether blockade of MHb nicotinic receptors has a direct effect on mesolimbic dopamine. Here, we performed in聽vivo microdialysis in female rats. Microdialysis probes were implanted into the nucleus accumbens (NAcc) and 伪3尾4 nicotinic receptor antagonists (18-methoxycoronaridine; 18-MC or 伪-conotoxin AuIB; AuIB), were injected into the ipsilateral MHb, just prior to systemic nicotine (0.4聽mg/kg, s.c.). Dialysate samples were collected before and after drug administration and levels of extracellular dopamine and its metabolites were measured using HPLC. Acute nicotine administration increased levels of extracellular dopamine and its metabolites in the NAcc. Pre-treatment with intra-habenular AuIB or 18-MC prevented nicotine-induced increases in accumbal dopamine. Neither drug had an effect on nicotine-induced increases in dopamine metabolites, suggesting that 伪3尾4 receptors do not play a role in dopamine metabolism. The effect of intra-habenular blockade of 伪3尾4 receptors on NAcc dopamine was selective for acute nicotine: neither AuIB nor 18-MC prevented increases in NAcc dopamine stimulated by acute d-amphetamine or morphine. These results suggest the mesolimbic response to acute nicotine, but not to acute administration of other drugs of abuse, is directly modulated by 伪3尾4 nicotinic receptors in the MHb, and emphasize a critical role for habenular nicotinic receptors in nicotine's reinforcing effects.