We examined the interaction of ethanol with the ␥-aminobutyric acid (GABA)ergic system in neurons of slices of the rat central amygdala nucleus (CeA), a brain region thought to be critical for the reinforcing effects of ethanol. Brief superfusion of 11-66 mM ethanol significantly increased GABA type A (GABA A) receptormediated inhibitory postsynaptic potentials (IPSPs) and currents (IPSCs) in most CeA neurons, with a low apparent EC50 of 20 mM. Acute superfusion of 44 mM ethanol increased the amplitude of evoked GABAA IPSPs and IPSCs in 70% of CeA neurons. The ethanol enhancement of IPSPs and IPSCs occurred to a similar extent in the presence of the GABA type B (GABA B) receptor antagonist CGP 55845A, suggesting that this receptor is not involved in the ethanol effect on CeA neurons. Ethanol superfusion also decreased pairedpulse facilitation of evoked GABAA IPSPs and IPSCs and always increased the frequency and sometimes the amplitude of spontaneous miniature GABA A IPSCs as well as responses to local GABA application, indicating both presynaptic and postsynaptic sites of action for ethanol. Thus, the CeA is the first brain region to reveal, without conditional treatments such as GABAB antagonists, consistent, low-dose ethanol enhancement of GABAergic transmission at both pre-and postsynaptic sites. These findings add further support to the contention that the ethanol-GABA interaction in CeA plays an important role in the reinforcing effects of ethanol.alcohol ͉ GABA IPSP͞Cs ͉ paired-pulse facilitation ͉ miniature synaptic current ͉ electrophysiology T he amygdala formation is a complex of interconnected nuclei that has been implicated in various physiological functions such as attention (1), memory (1-4), emotion (5-7), and autonomic control (3). This complex has been linked to the motivational effects of drugs of abuse and alcoholism in particular (8).The ␥-aminobutyric acid (GABA)ergic system, particularly in the central amygdala nucleus (CeA), has been implicated in the expression of emotionality, including behavioral states of fear and anxiety, as well as states associated with consummatory responses (9). The CeA is considered to be crucial in mediating the behavioral effects of acute and chronic ethanol consumption (10, 11). Because stress reduction has long been considered to contribute to ethanol-seeking behavior in humans, researchers hypothesized that the CeA and its connections might be sites for a GABA-like action of ethanol to mediate ethanol reinforcement. Behavioral studies indicate that injection of GABAergic antagonists directly into the CeA decreases motivated responding for oral self-administration of ethanol in rats, whereas infusion of GABA agonists and benzodiazepines decreased anxiety (11,12). Thus, these studies suggest that GABAergic systems in the CeA play a major role in the acute reinforcing effects of ethanol (13) and in the anxiogenic response to ethanol withdrawal (14).There has been a continuing controversy over the ability of ethanol to enhance GABAergic neurotransmission [inhib...

The central amygdala (CeA) plays a role in the relationship among stress, corticotropin-releasing factor (CRF), and alcohol abuse. In whole-cell recordings, both CRF and ethanol enhanced gamma-aminobutyric acid-mediated (GABAergic) neurotransmission in CeA neurons from wild-type and CRF2 receptor knockout mice, but not CRF1 receptor knockout mice. CRF1 (but not CRF2) receptor antagonists blocked both CRF and ethanol effects in wild-type mice. These data indicate that CRF1 receptors mediate ethanol enhancement of GABAergic synaptic transmission in the CeA, and they suggest a cellular mechanism underlying involvement of CRF in ethanol's behavioral and motivational effects.

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mCM may be a useful adjunctive smoking cessation treatment component for reducing smoking among smokers with PTSD, particularly early in a smoking quit attempt.

Immunocytochemical and electrophysiological evidence suggests that somatostatin may be a transmitter in the hippocampus. To characterize the ionic mechanisms underlying somatostatin effects, voltage-clamp and current-clamp studies on single CA1 pyramidal neurons in the hippocampal slice preparation were performed. Both somatostatin-28 and somatostatin-14 elicited a steady outward current and selectively augmented the noninactivating, voltage-dependent outward potassium current known as the M-current. Since the muscarinic cholinergic agonists carbachol and muscarine antagonized this current, these results suggest a reciprocal regulation of the M-current by somatostatin and acetylcholine.

The presence and severity of PTSD in veterans were associated with greater physical health problems and conditions. Psychological variables (e.g., PTSD status, PTSD severity, somatization) and a behavioral variable (pack-year history) were related to health status.

Summary Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social-defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions.