The effects of nicotinamide on reinstatement to cocaine seeking in male and female Sprague Dawley rats

Rationale Interventions for psychostimulant use disorders are of significant need. Nicotinamide (NAM) is a small molecule that can oppose cellular adaptations observed following cocaine exposure in the rodent self-administration and reinstatement model of addiction. In addition, utility of NAM against symptoms of withdrawal and vulnerability to relapse to cocaine use has been suggested by case studies and anecdotal reports. However, the empirical effects of NAM on drug-seeking behaviors have not been examined. Objective The objective of the current study was to investigate the effects of systemic NAM administration on reinstatement to cocaine seeking, using the rat self-administration/extinction/reinstatement model of cocaine addiction. Methods Male and female Sprague Dawley rats were trained to self-administer i.v. cocaine or food pellets for 2 hrs per day for 12 days, followed by 14-17 days of extinction, during which i.p. NAM injections (0-120 mg/kg) were given 30 minutes prior to each extinction or reinstatement session. Rats were tested on cue-, cocaine-, or food-primed reinstatement, as well as locomotor activity. Results Chronic NAM administered throughout extinction dose dependently attenuated cue-primed reinstatement in male rats, but not female rats. In contrast, acute NAM given once prior to reinstatement had no effect on reinstatement. Chronic NAM had no effect on locomotor activity or reinstatement to food seeking. Conclusions The specificity of NAM against cue-primed reinstatement indicates that NAM may influence responsiveness to drug-associated cues, specifically in males. Future studies will examine the mechanism(s) by which NAM may exert this effect.