Dopaminergic and GABAergic Regulation of Alcohol‐Motivated Behaviors: Novel Neuroanatomical Substrates

Abstract

An understanding of the neuroanatomical substrates, neurocircuitry, and interaction of the neuronal systems which regulate alcohol drinking is key in the identification of novel targets for drugs to treat alcoholism in humans. In the present review novel substrates and circuitry within the dopaminergic and GABAergic systems which regulate alcohol motivated‐behaviors are discussed.

Early life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABAA mechanism

“…However, 3-PBC was shown to be a safe ligand devoid of untoward effects when given orally and did not work additively/synergistically with alcohol, or other benzodiazepine agonists (Harvey et al, 2002, June and Eiler, 2007). Hence, therapeutically, 3-PBC may represent a safe ligand to evaluate for stress-induced binge drinking and cognitive impulsivity induced by stressful life events such as childhood trauma.…”

“…During the stabilization procedures, the animals were never deprived of food or fluid. These procedures are well established in our laboratory (June and Eiler, 2007, Liu et al, 2011). Other cohorts of rats were given a 3% [w/v] concentration of sucrose and trained in an identical manner under the FR1, then FR4, schedule.…”

Deficits in substance P mRNA levels in the CeA are inversely associated with alcohol‐motivated responding

“…During the second phase of the training, animals lever-pressed for an EtOH + sucrose cocktail mixture under an FR1 schedule. Subsequently, the rats responded under an FR4 schedule for EtOH [10% v/v] on both right and left levers until their responses stabilized, defined as having daily responses within ± 20% of the average responses for five consecutive days (June, 2002; June and Eiler, 2007). Finally, two additional sets of rats [n = 5/locus] were trained to lever press for sucrose at the 2% [w/v] concentration such that reinforcer specificity in the experimental locus [i.e., CeA] and in the neuroanatomical control locus [i.e., CPu] could be evaluated at response rates which were similar to those for EtOH in CeA-microinfused animals.…”

Anxioselective anxiolytics: on a quest for the Holy Grail

“…The response to a drug in mice with a mutated, diazepam-insensitive α subunit (e.g., an α 2 (H101R) subunit), where a majority of these receptors are heterogeneous [70], could explain some of the discrepant findings between studies in these mice and pharmacological studies using subtype-selective agents. Some glaring examples of these discrepant findings include the anxiolytic-like actions of an α 3 preferring compound (TP 003) in both wild-type and knock-in mice carrying a mutated α 2 subunit [63], and the ability of the selective α 1 antagonist β-CCT (3- t- butoxy-β-carboline) [71] to block the anxiolytic-like (but not the muscle relaxant or ataxic) effects of BZs [72,73]. …”