A role for neuronal nicotinic acetylcholine receptors in ethanol-induced stimulation, but not cocaine- or methamphetamine-induced stimulation

Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA.
Psychopharmacology (Impact Factor: 3.88). 03/2008; 196(3):377-87. DOI: 10.1007/s00213-007-0969-7
Source: PubMed


Cocaine (COC), ethanol (EtOH), and methamphetamine (MA) are widely abused substances and share the ability to induce behavioral stimulation in mice and humans. Understanding the biological basis of behavioral stimulation to COC, EtOH, and MA may provide a greater understanding of drug and alcohol abuse.
In these studies we set out to determine if neuronal nicotinic acetylcholine receptors were involved in the acute locomotor responses to these drugs, our measure of behavioral stimulation.
A panel of acetylcholine receptor antagonists was used to determine if nicotinic receptors were involved in EtOH- and psychostimulant-induced stimulation. We tested the effect of these drugs in genotypes of mice (FAST and DBA/2J) that are extremely sensitive to this drug effect. To determine which acetylcholine receptor subunits may be involved in this response, relative expression of the alpha3, alpha6, beta2, and beta4 subunit genes was examined in mice selectively bred for high and low response to EtOH.
Mecamylamine, but not hexamethonium, attenuated the acute locomotor response to EtOH. The acetylcholine receptor antagonist dihydro-beta-erythroidine and methyllycaconitine had no effect on this response. The alpha6 and beta4, but not alpha3 or beta2, subunits of the acetylcholine receptor were differentially expressed between mice bred for extreme differences in EtOH stimulation. Mecamylamine had no effect on psychostimulant-induced locomotor activity.
Neuronal nicotinic receptors are involved in EtOH, but not psychostimulant, stimulation. These studies suggest a lack of involvement of some nicotinic receptor subtypes, but more work is needed to determine the specific receptor subtypes involved in this behavior.

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Available from: Helen Kamens, Aug 19, 2014
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    • "In addition, recent pharmacological studies have implicated a3b4 nAChR in ethanol consumption and seeking in rats (Chatterjee et al., 2011) as well as in alcohol and nicotine co-dependencies (Bito-Onon, Simms, Chatterjee, Holgate, & Bartlett, 2011). Also, the non-specific nAChR antagonist mecamylamine attenuates ethanol-induced stimulation in DBA/2J mice (Kamens & Phillips, 2008). Although mecamylamine is regarded as non-specific, low doses of this nAChR antagonist have been shown to be more specific for a3b4 nAChR (Papke, Sanberg, & Shytle, 2001). "
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    • "injections of mecamylamine a comparatively low dose of 3 ␮g was used since higher doses have been reported to have unspecific effects, for example on the N-methyl-D-aspartate (NMDA) receptor (O'Dell and Christensen, 1988; Papke et al., 2001). Hexamethonium (Sigma-Aldrich , Munich, Germany) was dissolved in normal saline and administered at 2 mg/kg i.p., in a volume of 1 ml/kg, a dose used previously in comparative studies with mecamylamine of central and peripheral effects of nAChR signaling (Tani et al., 1997; Kamens and Phillips, 2008). All central injections were performed using a microinfusion pump (CMA 400 syringe pump, Solna, Sweden). "
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