Modulation of serotonin and noradrenaline in the BLA by pindolol reduces long-term ethanol intake.

Repeated cycles of binge-like alcohol consumption and abstinence change the activity of several neurotransmitter systems. Some of these changes are consolidated following prolonged alcohol use and are thought to play an important role in the development of dependence. We have previously shown that systemic administration of the dual beta-adrenergic antagonist and 5-HT partial agonist pindolol selectively reduces long-term but not short-term binge-like consumption of ethanol and alters excitatory postsynaptic currents in basolateral amygdala (BLA) principal neurons.

Sex Specific Alterations in α4*Nicotinic Receptor Expression in the Nucleus Accumbens.

: The mechanisms leading from traumatic stress to social, emotional and cognitive impairment and the development of mental illnesses are still undetermined and consequently there remains a critical need to develop therapies for preventing the adverse consequences of traumatic stress. Research indicates nicotinic acetylcholine receptors containing α4 subunits (α4*nAChRs) are both impacted by stress and capable of modulating the stress response. In this study, we investigated whether varenicline, a partial α4β2*nAChR agonist which reduces nicotine, alcohol and sucrose consumption, can reduce stress, a driving factor in substance use disorders.

Social and environmental enrichment has different effects on ethanol and sucrose consumption in mice.

Background: Factors leading to the harmful consumption of substances, like alcohol and sucrose, involve a complex interaction of genes and the environment. While we cannot control the genes we inherit, we can modify our environment. Understanding the role that social and environmental experiences play in alcohol and sucrose consumption is critical for developing preventative interventions and treatments for alcohol use disorders and obesity.

The effect of varenicline on binge-like ethanol consumption in mice is β4 nicotinic acetylcholine receptor-independent.

Background: Our laboratory has previously shown that the smoking-cessation agent varenicline, an agonist/partial agonist of α4β2*, α3β4*, α3β2*, α6β2* (* indicates the possibility of additional subunits) and α7 subunits of nicotinic acetylcholine receptors (nAChRs), reduces ethanol consumption in rats only after long-term exposure (12 weeks). As compounds having partial agonistic activity on α3β4* nAChRs were shown to decrease ethanol consumption in rodents, we assessed here the involvement of the β4 subunit in the effect of varenicline in the reduction of short- and long-term binge-like ethanol drinking in mice.

Methods: We used the well-validated drinking-in-the-dark (DID) paradigm to model chronic binge-like ethanol drinking in β4 and β4 littermate mice and compare the effect of intraperitoneal injection of varenicline (2mg/kg) on ethanol intake following short- (4 weeks) or long-term (12 weeks) exposure.

The antihypertensive drug pindolol attenuates long-term but not short-term binge-like ethanol consumption in mice.

Alcohol dependence is a debilitating disorder with current therapies displaying limited efficacy and/or compliance. Consequently, there is a critical need for improved pharmacotherapeutic strategies to manage alcohol use disorders (AUDs). Previous studies have shown that the development of alcohol dependence involves repeated cycles of binge-like ethanol intake and abstinence.

Early Life Stress, Nicotinic Acetylcholine Receptors and Alcohol Use Disorders.

Stress is a major driving force in alcohol use disorders (AUDs). It influences how much one consumes, craving intensity and whether an abstinent individual will return to harmful alcohol consumption. We are most vulnerable to the effects of stress during early development, and exposure to multiple traumatic early life events dramatically increases the risk for AUDs.