Working Memory Performance Predicts, but Does Not Reduce, Cocaine and Cannabinoid Seeking in Adult Male Rats

Area of Science:

• Neuroscience
• Behavioral Science
• Psychiatry

Background:

• Cognitive deficits, particularly in executive function, are prevalent in psychiatric disorders and substance use.
• Cognitive training aims to enhance prefrontal cortex plasticity and executive control, potentially improving treatment outcomes.
• Brain-derived neurotrophic factor (BDNF) plays a role in prefrontal cortex plasticity and may reduce drug-seeking behaviors.

Purpose of the Study:

• To determine if working memory training increases BDNF levels in the prefrontal cortex.
• To investigate if working memory training predicts or protects against cocaine or cannabinoid seeking.

Main Methods:

• Adult male rats underwent "simple" or "complex" delayed-match-to-sample working memory task training.
• Rats then self-administered cocaine or a synthetic cannabinoid (WIN55,212-2) and were tested for cued drug seeking during abstinence.
• BDNF protein levels were analyzed in prefrontal cortex and dorsal hippocampus tissue.

Main Results:

• Working memory training elevated BDNF protein in the prelimbic prefrontal cortex, but not the dorsal hippocampus.
• Training did not affect self-administration of either drug.
• Working memory training predicted the extent of cannabinoid self-administration and cocaine seeking during abstinence.

Conclusions:

• Working memory training enhances endogenous BDNF in the prefrontal cortex.
• The training did not alter current drug-seeking or drug-taking behaviors.
• Pre-drug exposure cognitive performance may predict vulnerability to substance use.