Alpha 4 beta 2* nicotinic acetylcholine receptors modulate the effects of ethanol and nicotine on the acoustic startle response.

Background: Ethanol modulates the functional activity of alpha4beta2 neuronal nicotinic cholinergic receptors (nAChR) when measured in vitro, but the potential role of alpha4beta2 nAChRs in regulating behavioral effects of ethanol is unknown. Recently, Tritto et al. (Tritto T, Stitzel JA, Marks MJ, Romm E, Collins AC (2002) Variability in response to nicotine in the LSxSS RI strains: potential role of polymorphisms in alpha4 and alpha6 nicotinic receptor genes.

A polymorphism in the alpha4 nicotinic receptor gene (Chrna4) modulates enhancement of nicotinic receptor function by ethanol.

Background: Several studies indicate that ethanol enhances the activity of alpha4beta2 nicotinic acetylcholine receptors (nAChR). Our laboratory has identified a polymorphism in the alpha4 gene that results in the substitution of an alanine (A) for threonine (T) at amino acid position 529 in the second intracellular loop of the alpha4 protein. Mouse strains expressing the A variant have, in general, greater nAChR-mediated 86Rb+ efflux in response to nicotine than strains with the T variant.

Inbred mouse strain differences in the establishment of long-term fear memory.

Studies describing variations in fear-related memory in inbred mouse strains typically focus upon 24 h retention. As a consequence, little is known about strain differences in the establishment of longer lasting memories of aversive events. In the present study, male mice from the strains A/Ibg, AKR/J, BALB/cByJ, CBA/J, C3H/HeIbg, C57BL/6J, DBA/2J, LP/J, SJL/J and 129/SvevTac were tested 24 h, 14, or 60 days after contextual and auditory-cued fear conditioning.

Contextual and cued fear conditioning in C57BL/6J and DBA/2J mice: context discrimination and the effects of retention interval.

Context discrimination and time course studies of contextual fear conditioning revealed strain differences between C57BL/6J (B6) and DBA/2J (D2) mice. Both strains discriminated contexts, but D2 mice exhibited less freezing in a shock-paired context. The strains did not differ immediately, or at 1 and 3 hr after contextual fear conditioning training.

A polymorphism in the mouse neuronal alpha4 nicotinic receptor subunit results in an alteration in receptor function.

Nicotine-stimulated (86)Rb(+) efflux and [(3)H]cytisine binding, both of which seem to measure the nicotinic acetylcholine receptor, composed of alpha4 and beta2 subunits, were assessed in eight brain regions obtained from 14 inbred mouse strains. The potential role of a single nucleotide polymorphism (SNP) in the nicotinic receptor alpha4 subunit gene (Chrna4) on nicotinic receptor binding and function in mice was also evaluated. This SNP leads to an alanine-to-threonine variation at amino acid position 529 of the nascent alpha4 subunit polypeptide.