Alcohol Modulates Frontal Cortex and BLA Network States Which Correlate with Future Voluntary Alcohol Consumption.

Although most adults in the United States will drink alcohol in their life, only ∼6% will go on to develop an alcohol use disorder (AUD). While a great deal of work has furthered our understanding of the cycle of addiction, it remains unclear why certain people transition to disordered drinking. Altered activity in regions implicated in AUDs, like the basolateral amygdala (BLA), has been suggested to play a role in the pathophysiology of AUDs, but how these networks contribute to alcohol misuse remains unclear.

Network States in the Basolateral Amygdala Predicts Voluntary Alcohol Consumption.

Unlabelled: Although most adults in the United States will drink alcohol in their life, only about 6% will go on to develop an alcohol use disorder (AUD). While a great deal of work has furthered our understanding of the cycle of addiction, it remains unclear why certain people transition to disordered drinking. Altered activity in regions implicated in AUDs, like the basolateral amygdala (BLA), has been suggested to play a role in the pathophysiology of AUDs, but how these networks contribute to alcohol misuse remains unclear.

Impaired Endogenous Neurosteroid Signaling Contributes to Behavioral Deficits Associated With Chronic Stress.

Background: Chronic stress is a major risk factor for psychiatric illnesses, including depression. However, the pathophysiological mechanisms whereby stress leads to mood disorders remain unclear. Allopregnanolone acts as a positive allosteric modulator preferentially on δ subunit-containing GABA (gamma-aminobutyric acid A) receptors.

Sex Differences in the Alcohol-Mediated Modulation of BLA Network States.

Alcohol use, reported by 85% of adults in the United States, is highly comorbid with mood disorders, like generalized anxiety disorder and major depression. The basolateral amygdala (BLA) is an area of the brain that is heavily implicated in both mood disorders and alcohol use disorder. Importantly, the modulation of BLA network/oscillatory states via parvalbumin (PV)-positive GABAergic interneurons has been shown to control the behavioral expression of fear and anxiety.

Pituitary adenylate cyclase-activating polypeptide type 1 receptor within the nucleus accumbens core mediates excessive alcohol drinking in alcohol-preferring rats.

Alcohol use disorders (AUD) have a strong component of heritability; however, the neurobiological mechanisms mediating the propensity to consume excessive amounts of alcohol are still not well understood. Pituitary adenylate cyclase-activating polypeptide (PACAP), a highly conserved neuropeptide which exerts its effects mainly through the PAC1 receptor (PAC1R), has been suggested to be one of the mediators of the effects of drugs of abuse and alcohol. Here, we investigated the role of the PACAP/PAC1R system in excessive alcohol drinking in alcohol-preferring rats, an established animal model of AUD.

Neurobiological Bases of Alcohol Consumption After Social Stress.

The urge to seek and consume excessive alcohol is intensified by prior experiences with social stress, and this cascade can be modeled under systematically controlled laboratory conditions in rodents and non-human primates. Adaptive coping with intermittent episodes of social defeat stress often transitions to maladaptive responses to traumatic continuous stress, and alcohol consumption may become part of coping responses. At the circuit level, the neural pathways subserving stress coping intersect with those for alcohol consumption.

Sigma receptor-induced heavy drinking in rats: Modulation by the opioid receptor system.

Alcohol use disorder (AUD) is a major cause of morbidity and mortality worldwide, for which new efficacious treatments are necessary. The opioid receptor system is a mediator of the rewarding effects of alcohol; in particular, while activation of μ opioid receptors enhances ethanol intake in rodents, opioid-receptor antagonists, such as naloxone and naltrexone, reduce its pleasurable and reinforcing effects, thereby decreasing alcohol. Sigma receptors (Sig-Rs) have been proposed as modulators of the effects of alcohol and, therefore, as a potential new pharmacological target for AUD.

Circuit directionality for motivation: Lateral accumbens-pallidum, but not pallidum-accumbens, connections regulate motivational attraction to reward cues.

Sign-tracking behavior, in which animals interact with a cue that predicts reward, provides an example of how incentive salience can be attributed to cues and elicit motivation. The nucleus accumbens (NAc) and ventral pallidum (VP) are two regions involved in cue-driven motivation. The VP, and NAc subregions including the medial shell and core, are critical for sign-tracking.

Subsecond fear discrimination in rats: adult impairment in adolescent heavy alcohol drinkers.

Discriminating safety from danger must be accurate and rapid. Yet, the rapidity with which fear discrimination emerges remains unknown. Rapid fear discrimination in adulthood may be susceptible to impairment by adolescent heavy alcohol drinking, which increases incidence of anxiety disorders.

Ethanol-related behaviors in mice lacking the sigma-1 receptor.

Rationale: The Sigma-1 receptor (Sig-1R) is a chaperone protein that has been implicated in drug abuse and addiction. Multiple studies have characterized the role the Sig-1R plays in psychostimulant addiction; however, fewer studies have specifically investigated its role in alcohol addiction. We have previously shown that antagonism of the Sig-1R reduces excessive drinking and motivation to drink, whereas agonism induces binge-like drinking in rodents.

Early adversity disrupts the adult use of aversive prediction errors to reduce fear in uncertainty.

Early life adversity increases anxiety in adult rodents and primates, and increases the risk for developing post-traumatic disorder (PTSD) in humans. We hypothesized that early adversity impairs the use of learning signals -negative, aversive prediction errors-to reduce fear in uncertainty. To test this hypothesis, we gave adolescent rats a battery of adverse experiences then assessed adult performance in probabilistic Pavlovian fear conditioning and fear extinction.

Alcohol gains access to appetitive learning through adolescent heavy drinking.

Adolescent heavy alcohol drinking increases the risk for alcohol use disorders in adulthood, yet mechanisms conferring increased risk are not well understood. We propose that adolescent alcohol drinking shapes alcohol's aversive or appetitive properties in adulthood. Alcohol normally drives aversive learning and alcohol-predictive cues are avoided.