Involvement of the medial septum in stress-induced relapse to heroin seeking in rats

Intermittent footshock stress has been shown to reinstate extinguished drug -taking behaviour in rats, but the brain areas involved in this effect are to a large degree unknown. Here we studied the role of the septum in stress -induced reinstatement of heroin seeking. Rats were trained to self-adminis ter heroin for 9-10 days (three 3-h sessions per day, 0.1 mg/kg per infusio n). Following training, extinction sessions were given for 8-13 days by sub stituting saline for heroin, and then tests for reinstatement of heroin see king were carried out. Reversible inactivation of the medial septum with te trodotoxin (TTX; 1-5 ng, infused 25-40 min before the test sessions) reliab ly reinstated heroin seeking, mimicking the effect of 15 min of intermitten t footshock. This effect of TTX was not observed after infusions made 1.5 m m dorsally into the lateral septum. In other experiments, it was found that infusions of a low, subthreshold dose of TTX (0.5 ng) into the medial sept um, when combined with 2 min of footshock that in itself was ineffective, r einstated heroin seeking. Furthermore, electrical stimulation (400 mu A pul ses, 100 mu s duration, 100 Hz frequency) of the medial septum during expos ure to 10 min of intermittent footshock attenuated footshock-induced reinst atement of heroin seeking. These data suggest a role for the medial septum in stress-induced relapse to drug seeking. The septum is thought to be invo lved in neuronal processes underlying behavioural inhibition, thus we specu late that stressors provoke relapse by interfering with these processes.