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Central among the brain regions that regulate fear/anxiety behaviors is the lateral/basolateral amygdala (BLA). BLA output is tightly controlled by the relative activity of two populations of inhibitory GABAergic interneurons, local feed-back cells distributed throughout the nucleus and feed-forward cells found along the lateral paracapsular border of this subdivision. Recent studies suggest that dopamine can modulate the BLA GABAergic system thus linking fear/anxiety-states with mesolimbic reward/attentional processes. However, the precise dopaminergic mechanisms regulating the activity of the two BLA GABAergic neuron populations have not been fully explored. We therefore examined the effects of dopamine (DA) D3-like receptors on BLA-dependent anxiety-like behavior and neurophysiology. After confirming the presence of D3-like receptors within the BLA, we found that microinjection of a D3-selective antagonist into the BLA decreased anxiety-like behavior expressed in both the light/dark transition test and the elevated plus maze. Consistent with this, we found that in vitro D3-like receptor activation selectively inhibits synaptic transmission at both BLA feed-back and feed-forward GABAergic interneuron populations, with no effect on glutamatergic transmission. This inhibition of GABAergic transmission is a result of a D3-like receptor-mediated, dynamin-dependent process that presumably reflects endocytosis of postsynaptic GABAA receptors found on principal BLA neurons. Because environmental cues alter both DA release and relative activity states of the BLA, our data strongly suggest that DA, potentially acting through D3-like receptors, may suppress the relative contribution by inhibitory processes in the BLA and modify the expression of BLA-related behaviors.

Withdrawal-related anxiety is cited as a major contributor to relapse in recovering alcoholics. Changes in lateral/basolateral amygdala (BLA) neurotransmission could directly influence anxiety-like behaviors after chronic ethanol exposure and withdrawal. We have shown that these treatments enhance BLA glutamatergic function and neurotransmission. However, the BLA GABAergic system tightly controls the expression of anxiety-like behavior, and additional neuroadaptations in this system are potentially important as well. The intrinsic BLA GABAergic system consists of at least two populations of interneurons: local feed-back interneurons scattered throughout the region and feed-forward interneurons concentrated within groups found in the lateral/paracapsular region of the BLA. In the present study, we found that withdrawal from chronic ethanol robustly decreased presynaptic function at feed-forward GABA synapses but did not alter neurotransmitter release from local interneurons. Differential presynaptic changes at these synapses were complemented by decreased zolpidem sensitivity at feed-forward synapses and decreased midazolam sensitivity at local synapses. Consistent with this, chronic ethanol/ withdrawal decreased expression of GABA ␣1-subunit total protein and increased surface expression of ␣4-subunit protein. We also found transient increases in GABA-receptor-associated protein levels and persistent increases in ␥2-subunit and gephyrin proteins that would suggest alterations in GABA A receptor trafficking that might help regulate changes in ␣4-subunit localization. These data together suggest that chronic ethanol and withdrawal differentially modulate local and lateral paracapsular cell GABAergic synapses via distinct presynaptic and postsynaptic mechanisms. These findings extend our understanding of the neurobiological mechanisms governing changes in anxiety-like behavior after chronic ethanol exposure and withdrawal.

The stability and multivariate effects of life stress, social support, and anxiety from mid to late pregnancy in a sample of low-income women were examined. The sample of 190 was approximately equally divided among black, Hispanic, and white groups. Scores from the two time periods were highly consistent. The multivariate effects of life stress and social support on anxiety were similar at the two time periods, explaining 30% to 34% of the variance in anxiety, over and above the effects of ethnicity or marital status. The prospective test (Time 1 variables predicting Time 2 anxiety), however, explained only 22% of the variance in anxiety. Significant stress-buffering effects from social support were found for both the Time 1 regression and the prospective test. The combination of high life stress and low partner support was associated with the highest anxiety. The findings confirmed that mid-pregnancy measures of these psychosocial variables were valid indicators of their level over the course of the remainder of the pregnancy, allowing for early assessment and intervention to improve perinatal well-being.

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