Discriminative Stimulus Effects of Ethanol in C57BL/6J and DBA/2J Inbred Mice

Abstract

The initial stimulus effects of 1.5 g/kg ethanol may be more salient in D2 than B6 mice. This does not appear to result from differences in the neurotransmitter systems that mediate ethanol's discriminative stimulus effects. In both strains, gamma-aminobutyric acid-positive modulators and a noncompetitive NMDA antagonist substituted for ethanol. However, strain differences did exist in the potency of gamma-aminobutyric acid-positive modulators and morphine for suppressing operant responding.

Pharmacological and Anatomical Evidence for an Interaction Between mGluR5- and GABAA α1-Containing Receptors in the Discriminative Stimulus Effects of Ethanol

“…Consistent with previous reports, pentobarbital (Ator et al, 1993;Grant et al, 1996;Hodge et al, 2001;Shelton and Grant, 2002) and diazepam (Jarbe and McMillan, 1983;Ator et al, 1993;Kostowski and Bienkowski, 1999;Green-Jordan and Grant, 2000;Shelton and Grant, 2002) dose dependently substituted for the stimulus effects of ethanol. MPEP pretreatment did not alter pentobarbital (1-10 mg/kg) substitution for ethanol.…”

“…The discriminative stimulus effects of ethanol are mediated in part by positive modulation of GABA A receptor activity (Ator et al, 1993;Grant and Lovinger, 1995;Hodge and Cox, 1998;Kostowski and Bienkowski, 1999;Hodge et al, 2001;Shelton and Grant, 2002). Evidence indicates that mGlu5 receptors can modulate GABA A receptor function (Awad et al, 2000;Hoffpauir and Gleason, 2002) and extracellular GABA levels.…”

“…For example, positive modulators of GABA A receptors, such as barbiturates, benzodiazepines, and neurosteroids, produce ethanollike stimulus effects (Ator et al, 1993;Barry, 1991;Evans and Balster, 1991;Grant et al, 1996Grant et al, , 1997Jarbe and McMillan, 1983;Shelton and Grant, 2002) in multiple species. MGluR5 activity has the potential to influence ethanol discrimination based on evidence that mGluR5 can influence GABA neurotransmission (de Novellis et al, 2003;Hoffpauir and Gleason, 2002;Diaz-Cabiale et al, 2002).…”

Activation of Group II Metabotropic Glutamate Receptors Inhibits the Discriminative Stimulus Effects of Alcohol via Selective Activity Within the Amygdala

“…As such, activation of mGlu2/3 receptors decreases the synaptic availability of glutamate, allowing for 'refinement' of glutamatergic neurotransmission (Schoepp, 2001;Pinheiro and Mulle, 2008). Given the functional role of mGlu2/3 receptors in modulating glutamate release and that the discriminative stimulus effects of alcohol are generally characterized by processes that reduce/inhibit glutamatergic neurotransmission (Kostowski and Bienkowski, 1999), such that N-methyl-Daspartic acid (NMDA) antagonists and g-aminobutyric acid type A (GABA A )-positive modulators produce alcohol-like discriminative stimulus effects (Jarbe and McMillan, 1983;Schechter et al, 1993;Ator et al, 1993;Bienkowski et al, 1997;Hundt et al, 1998;Grant et al, 2000;Shelton and Grant, 2002;Vivian et al, 2002;Helms et al, 2009), we hypothesized that mGlu2/3 receptors may have a modulatory role in the expression of the discriminative stimulus effects of alcohol. Further support for this hypothesis comes from studies showing that mGlu2/3 receptors are highly expressed in limbic brain regions (Petralia et al, 1996;Ohishi et al, 1998;Ferraguti and Shigemoto, 2006) known to modulate the discriminative stimulus effects of alcohol, such as the nucleus accumbens and the amygdala (Hodge and Aiken, 1996;Hodge and Cox, 1998;Hodge et al, 2001;Besheer et al, 2003).…”

Amphetamine Primes Motivation to Gamble and Gambling-Related Semantic Networks in Problem Gamblers

“…Research with animals further indicates that the discriminative stimulus properties of alcohol are unlike those of AMPH (Druhan et al, 1991). The AMPH stimulus primarily involves mono-amine activation (Brauer et al, 1997;Furmidge et al, 1991;Ranaldi et al, 2000;Sasaki et al, 1995), whereas the alcohol stimulus primarily involves GABA-A activation and glutamate inhibition (Jackson et al, 2003;Kostowski and Bienkowski, 1999;Shelton and Grant, 2002;Stolerman and Olufsen, 2001), along with some serotonergic elements (Maurel et al, 1997). In animal studies, systemic AMPH, at a range of doses, does not reliably prime alcohol seeking in animals familiar with alcohol (Halladay et al, 1999;Hubbell et al, 1991;Linseman, 1990), but consistently primes seeking of another psychostimulantFcocaineFin animals familiar with cocaine (de Wit and Stewart, 1981;Lynch et al, 1998;Schenk and Partridge, 1999).…”