title: Nicotine administration in the wake-promoting basal forebrain attenuates sleep-promoting effects of alcohol.
abstract: Nicotine and alcohol co-abuse is highly prevalent, although the underlying causes are unclear. It has been suggested that nicotine enhances pleasurable effects of alcohol while reducing aversive effects. Recently, we reported that nicotine acts via the basal forebrain (BF) to activate nucleus accumbens and increase alcohol consumption. Does nicotine suppress alcohol-induced aversive effects via the BF? We hypothesized that nicotine may act via the BF to suppress sleep-promoting effects of alcohol. To test this hypothesis, adult male Sprague-Dawley rats were implanted with sleep-recording electrodes and bilateral guides targeted toward the BF. Nicotine (75 pmol/500 nL/side) or artificial cerebrospinal fluid (ACSF; 500 nL/side) was microinjected into the BF followed by intragastric alcohol (ACSF + EtOH and NiC + EtOH groups; 3 g/kg) or water (NiC + W and ACSF + W groups; 10 mL/kg) administration. On completion, rats were killed and processed to localize injection sites in the BF. The statistical analysis revealed a significant effect of treatment on sleep-wakefulness. While rats exposed to alcohol (ACSF + EtOH) displayed strong sleep promotion, nicotine pre-treatment in the BF (NiC + EtOH) attenuated alcohol-induced sleep and normalized sleep-wakefulness. These results suggest that nicotine acts via the BF to suppress the aversive, sleep-promoting effects of alcohol, further supporting the role of BF in alcohol-nicotine co-use.
authors.affiliation: Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA.|Department of Neurology, University of Missouri, Columbia, Missouri, USA.
authors.forename: Rishi
authors.initials: R
authors.lastname: Sharma
authors.affiliation: Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA.|Department of Neurology, University of Missouri, Columbia, Missouri, USA.
authors.forename: Shafi
authors.initials: S
authors.lastname: Lodhi
authors.affiliation: Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA.|Department of Neurology, University of Missouri, Columbia, Missouri, USA.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Sahota
authors.affiliation: Harry S. Truman Memorial Veterans Hospital, Columbia, Missouri, USA.|Department of Neurology, University of Missouri, Columbia, Missouri, USA.
authors.forename: Mahesh M
authors.initials: MM
authors.lastname: Thakkar
mesh_terms: D000818:Animals; D066187:Basal Forebrain; D002492:Central Nervous System Depressants / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D003700:Delta Rhythm / Q000187:drug effects; D004569:Electroencephalography / Q000187:drug effects; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects*; D012895:Sleep, REM / Q000187:drug effects; D014851:Wakefulness / Q000187:drug effects
chemical_list: D002492:Central Nervous System Depressants; D018722:Nicotinic Agonists; D000431:Ethanol; D009538:Nicotine
keywords: alcohol; basal forebrain; cholinergic; nicotine; rat; sleep