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

Abstract

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-administer heroin for 9-10 days (three 3-h sessions per day, 0.1 mg/kg per infusion). Following training, extinction sessions were given for 8-13 days by substituting saline for heroin, and then tests for reinstatement of heroin seeking were carried out. Reversible inactivation of the medial septum with tetrodotoxin (TTX; 1-5 ng, infused 25-40 min before the test sessions) reliably reinstated heroin seeking, mimicking the effect of 15 min of intermittent footshock. This effect of TTX was not observed after infusions made 1.5 mm 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 septum, when combined with 2 min of footshock that in itself was ineffective, reinstated heroin seeking. Furthermore, electrical stimulation (400 microA pulses, 100 micros duration, 100 Hz frequency) of the medial septum during exposure to 10 min of intermittent footshock attenuated footshock-induced reinstatement 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 involved in neuronal processes underlying behavioural inhibition, thus we speculate that stressors provoke relapse by interfering with these processes.

Intra-median raphe nucleus (MRN) infusions of muscimol, a GABA-A receptor agonist, reinstate alcohol seeking in rats: role of impulsivity and reward

“…Role of impulsivity in effects of muscimol on alcohol seeking Earlier studies on stress-induced reinstatement of drug and alcohol seeking suggested that stress might induce relapse to drug use by impairing the operation of an inhibitory behavioural control system (Highfield et al 2000;. The fact that intra-MRN injections of muscimol induce a variety of behaviours ranging from water Stratford and Wirtshafter 2000), food Wirtshafter 1988, 1989), and alcohol consumption (Tomkins et al 1994) and locomotor activity suggest that the projections originating in the MRN may be a part of such an inhibitory control system.…”

Social stress is as effective as physical stress in reinstating morphine-induced place preference in mice

“…One recent study demonstrates that only morphineconditioned withdrawal reinstates morphine CPP, which may be a stress-driven effect (Lu et al 2005). Thirdly, it has also been suggested that stress may provoke relapse by interfering with neuronal inhibitory processes, which inhibits responding when reinforcers are not available (Highfield et al 2000). In support of this idea, it has been observed that footshock stress increases resistance to extinction, and footshock's reinstating effects depend on the manipulation of the medial septum, a brain area involved in response inhibition (Highfield et al 2000).…”

Activation of Group II Metabotropic Glutamate Receptors in the Nucleus Accumbens Shell Attenuates Context-Induced Relapse to Heroin Seeking

“…The coordinates (Paxinos and Watson, 2005) for the NAc core (61 angle aimed medially) were AP + 1.6, ML72.5, and DVÀ6.0; coordinates for the NAc shell (61 angle aimed medially) were AP + 1.6, ML71.7, and DVÀ6.5; coordinates for the caudate-putamen (61 angle aimed medially) were AP + 1.6, ML72.5, and DVÀ4.5. Following cannulae implantation, silastic catheters were inserted into the jugular vein and were passed subcutaneously to the top of the skull, as described previously (Highfield et al, 2000;Shaham et al, 2000b). The catheters were then attached to a modified 22-gauge cannula (Plastics One, Roanoke, VA) and mounted to the rat's skull with dental cement.…”