Decreased brain reward produced by ethanol withdrawal

Area of Science:

• Neuroscience
• Addiction Research
• Behavioral Pharmacology

Background:

• Drug withdrawal syndromes, including from ethanol, opiates, and psychostimulants, share a common negative affective state in humans.
• Intracranial self-stimulation (ICSS) reward thresholds in rodents serve as a validated model for negative affective states during psychostimulant and opiate withdrawal.

Purpose of the Study:

• To investigate whether elevated ICSS reward thresholds are also present during ethanol abstinence.
• To establish a quantitative measure for the negative affective component of ethanol withdrawal.

Main Methods:

• Rats with lateral hypothalamic electrodes underwent chronic ethanol vapor exposure to induce physical dependence.
• ICSS thresholds were measured using a discrete-trial current-intensity procedure before and after ethanol cessation.
• Overt signs of withdrawal were also monitored and rated.

Main Results:

• A time-dependent elevation in ICSS thresholds was observed following ethanol withdrawal, peaking at 6-8 hours and lasting for 48 hours.
• Blood alcohol levels positively correlated with the magnitude of peak ICSS threshold elevation.
• Overt withdrawal signs exhibited a similar time course to ICSS threshold elevations.

Conclusions:

• Decreased reward system function, indicated by elevated ICSS thresholds, is a shared neurobiological feature across withdrawal from diverse drugs of abuse.
• ICSS threshold elevation provides a reliable animal model for the negative affective state associated with ethanol withdrawal.