α6β2 nicotinic acetylcholine receptors influence locomotor activity and ethanol consumption

Abstract

Nicotinic acetylcholine receptors (nAChRs) in the mesolimbic dopamine system have been implicated in ethanol behaviors. In particular, work in genetically engineered mice has demonstrated that α6-containing nAChRs are involved in ethanol consumption and sedation. A limitation of these studies is that the alteration in the receptor was present throughout development. The recently described α6β2 antagonist, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI), now makes it possible to test for the involvement of these receptors using a pharmacological approach. The aim of this study was to examine the role of α6β2 nAChRs in ethanol behaviors using a pharmacological approach. Adolescent C57BL/6J mice were treated with bPiDI 30 minutes prior to testing the mice for binge-like ethanol consumption in the drinking-in-the-dark (DID) test, ethanol-induced motor incoordination using the balance beam, and ethanol-induced sedation using the Loss of Righting Reflex (LORR) paradigm. Adolescent animals were chosen because they express a high amount of α6 mRNA relative to adult animals. Control studies were also performed to determine the effect of bPiDI on locomotor activity and ethanol metabolism. Female mice treated with 20 mg/kg bPiDI had reduced locomotor activity compared to saline-treated animals during the first 30 minutes following an acute injection. Pretreatment with the α6β2 antagonist reduced adolescent ethanol consumption but also reduced saccharin consumption. No significant effects were observed on ethanol-induced ataxia, sedation, or metabolism. This study provides evidence that α6β2 nAChRs are involved in locomotor activity as well as ethanol and saccharin consumption in adolescent animals.

Varenicline modulates ethanol and saccharin consumption in adolescent male and female C57BL/6J mice

“…Our work suggests that, in adolescence, varenicline has a non-specific effect on consumption because it reduces saccharin consumption in addition to ethanol. We recently reported similar findings with a α6β2 antagonist, N,N-decane-1,10-diyl-bis-3-picolinium diiodide (bPiDI) in adolescent mice (Kamens et al, 2017a). Specifically, we observed decreased ethanol and saccharin consumption providing evidence that α6β2 nAChRs may drive this effect in adolescent animals.…”

“…The effect of varenicline on ethanol consumption was tested with a 2-day drinking-in-the-dark (DID) procedure (Gupta et al, 2008; Kamdar et al, 2007; Kamens et al, 2017a). Briefly, naïve male and female mice (N = 24) were repeatedly tested in four 2-day DID sessions at postnatal days (PND) 32-33, 36-37, 39-40, and 43-44.…”

“…The primary dependent variable was ethanol consumption (g/kg). To ensure that the effect of varenicline was specific for ethanol, a naïve group of male and female adolescent C57BL/6J mice (N = 12/group) had access to 0.033% saccharin using the same procedure (Kamens et al, 2017a).…”

Adolescent social stress increases anxiety-like behavior and ethanol consumption in adult male and female C57BL/6J mice

“…The volume of fluid in the bottle (read to the closest 0.1 ml) was recorded immediately upon placement and at 2 h and 4 h. Immediately after the 4 h test, ~10–20 μl of blood was collected by tail nick, and blood ethanol concentrations (BEC) were measured using an Analox AM1 Analyzer (Analox Instruments, Lunenburg, MA). To ensure that the effect of adolescent CVSS was specific to ethanol, mice were retested with same procedure, but had access to 0.033% saccharin instead of ethanol 37 , 38 . For ethanol and saccharin consumption, two control cages with no mouse were handled with the same procedure as experimental cages.…”

Formulation, Characterization and Evaluation of Behavioral Effects of Suspension and Effervescent Granules of Evolvulus alsinoides Linn. and Convolvulus pluricaulis Choisy

“…34 ACh also affects the locomotor activity due to nicotinic acetylcholine receptors present in the mesolimbic dopaminergic system. 35 Scopolamine causes memory impairment and disturbed locomotor activity. 36,37 Piracetam is a standard drug used for cognition enhancement that improves the functioning of ACh and implicated in the memory process.…”