Nicotine Infusion in the Wake‐Promoting Basal Forebrain Enhances Alcohol‐Induced Activation of Nucleus Accumbens

Abstract

Background Nicotine and alcohol co-abuse is highly prevalent. Recently, we have shown that nicotine infusion in the basal forebrain (BF) increases alcohol consumption. Since nucleus accumbens (NAc) is the terminal brain region associated with drug addiction, we hypothesize that nicotine infusion in the BF may enhance alcohol induced activation of NAc. Methods Adult male Sprague-Dawley rats were surgically implanted with bilateral guide cannulas in the BF. Following post-operative recovery, rats were divided into four groups: 1) ACSF+W group received artificial cerebrospinal fluid (ACSF; 500 nl/side) in the BF and systemic water [intragastric (ig); 10 ml/kg; N=5], 2) EtOH group received ACSF in the BF (500 nL/side) and systemic alcohol (ig; 3 g/Kg; N=5), 3) NiC group received nicotine in the BF (75 pmole/500nl/side) and systemic water (ig; 10 mL/Kg; N=5) and 4) NiC+EtOH group received nicotine in the BF (75 pmole/500nl/side) and systemic alcohol (ig; 3 g/Kg; N=5). Rats were euthanized two hours after treatment to examine c-Fos expression in the NAc by immunohistochemistry. Results All injections sites were localized in the BF. Two way ANOVA (ig vs infusion) revealed significant main effects of both treatments (ig and infusion, p < 0.001) on c-Fos expression in the NAc shell but not in the core. Subsequent post-hoc test (Bonferroni’s) revealed that as compared to ACSF+W group, c-Fos expression was significantly increased in the shell of NAc of rats in all three (EtOH, NiC and NiC+EtOH) groups with maximal increase observed in NiC+EtOH group. Conclusions The results suggests: 1) BF nicotine infusion induced c-Fos in both core and the shell region of NAc at levels comparable to those observed after systemic alcohol administration; 2) BF nicotine infusion with systemic alcohol induced a significant additive increase in c-Fos expression only in the NAc shell region. These findings implicate the BF in alcohol and nicotine co-use.

Nicotine administration in the wake‐promoting basal forebrain attenuates sleep‐promoting effects of alcohol

“…; Sharma et al . ). Furthermore, in vitro studies using similar doses of nicotine have demonstrated nicotine induced neuronal activation in sleep‐wakefulness regulatory centers (Li et al .…”

“…The nicotine dose [75 pmol (equivalent to 11 ng of nicotine‐free base)/500 nl/side] was chosen based on our previous study in rats (Sharma et al . ).…”

“…We chose the 3 g/kg dose of alcohol because this dose of alcohol has robust effect on sleep promotion (Thakkar et al 2010b;Sharma et al 2014d). The nicotine dose [75 pmol (equivalent to 11 ng of nicotine-free base)/500 nl/side] was chosen based on our previous study in rats (Sharma et al 2014a).…”

Lesion of the basal forebrain cholinergic neurons attenuates sleepiness and adenosine after alcohol consumption

“…In contrast, pain is inherent with intraperitoneal route of alcohol administration. The 3 g/kg dose of alcohol was chosen because this dose is effective in promoting sleep and activating the reward centers Alaux-Cantin et al 2013;Sharma et al 2014a). The sleep promoting effects of alcohol was confirmed pre-lesion.…”

Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders

“…These studies also show that ethanol has differential effects on the NAc core and the shell. In the NAc shell ethanol alters dendrite morphology [ 54 ], cFos expression [ 55 ] and gamma amino butyric acid (GABA) [ 56 ] and dopamine [ 57 ] signaling. Whereas, in the NAc core ethanol exposure alters dendrite morphology [ 53 ], glutamate signaling [ 51 , 52 , 53 ] and mitogen-activated protein kinase (MAPK) expression [ 47 ].…”