Sign tracking predicts cue-induced but not drug-primed reinstatement to methamphetamine seeking in rats: Effects of oxytocin treatment

Background: The incentive sensitisation theory of addiction posits that drug-associated stimuli become imbued with incentive motivational properties, driving pathological drug seeking. However, pre-existing variability in the incentive salience to non-drug reward cues (‘sign trackers’ (STs); ‘goal trackers’ (GTs)) is also predictive of the desire for and relapse to cocaine and opioids. Here, we asked whether variation in propensity to attribute incentive salience to a food cue is predictive of reinstatement to the highly addictive psychostimulant methamphetamine (METH), and whether treatment with the promising anti-addiction therapy oxytocin differentially reduces METH behaviour between STs and GTs. Methods: Rats were trained to associate a Pavlovian cue with delivery of a sucrose pellet over 8 days. They then received jugular vein catheters for intravenous METH self-administration, followed by behavioural extinction, and cue-induced and METH-primed reinstatement to METH-seeking behaviours. Oxytocin was administered prior to self-administration and reinstatement tests. Results: Despite the self-administration of similar amounts of METH, STs reinstated more to METH cues than did GTs, yet METH-priming reinstated STs and GTs similarly. Furthermore, oxytocin attenuated cue-induced reinstatement more so in STs than in GTs, and reduced METH-primed reinstatement to a greater extent in the top quartile of reinstaters, indicating that oxytocin treatment may be most effective for those at highest risk of addiction. Conclusions: This pre-existing bias towards reward cues presents a possible tool to screen for METH addiction susceptibility and may be useful for understanding the neurobiology of addiction and for pharmacotherapeutic discovery.

Sucrose-Pellet Incentive Shifts in the Double Alley

4 groups of male albino rats were given 45 double runway trials under the following conditions: (a) nonreward in goal box (GB1) throughout, (b) nonreward in GB1 for 30 trials followed by an upshift to two 97-mg. sucrose pellets for 15 trials, (c) two 97-mg. sucrose pellets in GB1 throughout, or (d) two 97-mg. sucrose pellets for 30 trials followed by a GB1 downshift to nonreward for 15 trials. Sucrose incentive upshift produced a rapid runway one start speed increment, while the downshift in sucrose had little or no effect on this measure. Runway one run and goal measures and all measures of runway two performance seemed little affected by GB1 incentive magnitude, in that all groups converged toward a common asymptote.