GABA_A receptors containing α₁ and β₂ subunits are mainly localized on neurons in the ventral pallidum

Abstract

The gamma-aminobutyric acid (GABA) projection from the nucleus accumbens to the ventral pallidum (VP) is important in the regulation of locomotion. Thus, stimulation and inhibition of GABAA receptors in the VP can alter locomotor activity. To determine whether the GABAA receptors are located presynaptically on accumbens efferents to the VP or postsynaptically on neurons intrinsic to the VP two experiments were performed. In the first, quinolinic acid lesions of the nucleus accumbens did not alter [3H]muscimol binding in the VP, while lesions in the VP significantly reduced (60-80%) binding as measured by light microscopic receptor autoradiography. In the second experiment, in situ hybridization with oligonucleotide probes for mRNAs of the alpha 1 and beta 2 subunits of the GABAA receptor was examined in the nucleus accumbens and VP. No mRNA for either subunit was observed in the nucleus accumbens, although many positively labeled neurons were present within the VP. By contrast, a moderate to high density of cells in both the nucleus accumbens and VP contained mRNA for glutamic acid decarboxylase. These data argue that the majority of GABAA receptors in the VP are not located presynaptically on axonal terminals originating from neurons in the nucleus accumbens.

Distribution of the major γ‐aminobutyric acidA receptor subunits in the basal ganglia and associated limbic brain areas of the adult rat

“…In contrast to the case in the neostriatum (striatum and nucleus accumbens) and olfactory tubercle, subunit ␣1-, ␤2-, ␥1-, and ␥2-IR are prominent in the pallidal areas. Dense dendritic plexi are labeled with these subunit IR, and the respective mRNAs are expressed at high concentrations in pallidal neurons (Churchill et al, 1991;Wisden et al, 1992). Churchill et al (1991) provided evidence for a dendritic localization of subunits ␣1 and ␤2 in neurons of the ventral pallidum.…”

“…Dense dendritic plexi are labeled with these subunit IR, and the respective mRNAs are expressed at high concentrations in pallidal neurons (Churchill et al, 1991;Wisden et al, 1992). Churchill et al (1991) provided evidence for a dendritic localization of subunits ␣1 and ␤2 in neurons of the ventral pallidum. Colocalization studies revealed that the ␣1, ␤2/␤3, and ␥2 subunits are found together in neurons of the globus pallidus and the substantia nigra pars reticulata (Fritschy and Mohler, 1995;Somogyi et al, 1996).…”

Dopamine and Benzodiazepine-Dependent Mechanisms Regulate the EtOH-Enhanced Locomotor Stimulation in the GABAA α1 Subunit Null Mutant Mice

“…Several potential hypotheses, however, could account for these effects. First, in the absence of the a1 inhibitory sedative influences in CNS brain loci (eg, cortex, thalamus, hypothalamus, hippocampus, amygdala, ventral pallidum, midbrain, cerebellum) (Churchill et al, 1991;Fritschy and Mohler, 1995;Pirker et al, 2000), the EtOH-induced stimulation maybe unmasked and more readily observed. Second, it is possible elevation of a2 and a3 receptors in mesolimbic loci (eg, cortex, hypothalamus, hippocampus, amygdala, nucleus accumbens, VTA, bed nucleus of the stria terminalis (BST), etc.)…”

Binge Drinking: In Search of its Molecular Target via the GABAA Receptor

“…Of the potential GABA A receptors, substantial evidence implicates the α1 subunit-containing receptors in regulating excessive alcohol drinking (Harvey et al, 2002; June et al, 2003; June and Eiler, 2007). Thus, pharmacological studies demonstrate that microinfusion of α1-preferring ligands into the ventral pallidum (VP, a locus containing the highest concentrations of α1 subunits within the reward circuitry; Churchill et al, 1991) selectively regulates excessive alcohol drinking (June et al, 2003; Harvey et al, 2002; June and Eiler, 2007). Furthermore, the GABA-enhancing effects of alcohol in the VP were positively correlated with binding of the α1 selective agonist [ 3 H]zolpidem, and increased zolpidem binding has been reported in the VP of alcohol-preferring rats (Criswell et al, 1995; Devaud et al, 1995).…”