Figure 6.

Simplified schematic of rodent CeA circuitry and hypothetical sites of ethanol and NPY action on GABAergic synapses. Most neurons in the CeA are GABAergic inhibitory projection neurons or interneurons that co-transmit GABA and one of several neuromodulators, including NPY and CRF. Ethanol may enhance the release of GABA from GABAergic afferent neurons via direct activation of CRF₁ receptors on those afferents (17), but regardless of the mechanism of action, CRF and ethanol both likely inhibit the activity of GABAergic neurons projecting out of CeA. Conversely, activation of presynaptic Y₂ receptors by NPY reduces inhibition of GABAergic neurons projecting out of CeA, thereby facilitating the release of GABA onto downstream targets. These results are important because the interplay of CRF and NPY actions in CeA was previously identified to be important for the co-regulation of emotionality and anxiety (42). Therefore, recorded increases in GABAergic transmission (e.g., by CRF and ethanol) likely reflect a disinhibition of downstream target regions (e.g., BNST, hypothalamus, periaqueductal gray), whereas recorded decreases in GABAergic transmission (e.g., by NPY) reflect a net inhibition of downstream target regions. This hypothesis is supported not only by the behavioral effects of NPY in CeA (e.g., decreases in anxiety and decreases in alcohol drinking; 7, 10, 11), but also by recent data regarding CRF (17), nociceptin (18), vasopressin (43), and endocannabinoid (44) effects on cellular function in the rat CeA. Further details of this circuitry remain to be elucidated.