Min Of Footshock Research Articles

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-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.

Biochemical mechanisms of stress-induced impairment of rat T cell mitogenesis

Splenic mononuclear cells isolated from rats exposed to two brief stressors (5 min of restraint or 2 min of footshock) showed a diminished response to the T cell mitogens, concanavalin A and phytohemagglutinin. Cells from these stressed animals also exhibited a diminished response to stimulation with the phorbol ester, tetradecanoylphorbol acetate (TPA), and/or the calcium ionophore, ionomycin. Since stimulation with these latter two agents mimics early signals generated by mitogen surface receptor binding including increased intracellular calcium and protein kinase C activation, the data indicate that stress-related defects in T cell proliferation occur at sites other than or in addition to these early events in cellular activation.

Stress-induced alterations in plasma catecholamines and behavior of rats: Effects of chlorisondamine and bretylium

The response of the sympathetic nervous system and the adrenal medulla was examined in rats subjected to the stress of handling and transfer to a shock chamber and to the stress of 5 min of intermittent footshock. Ganglionic blockade with chlorisondamine chloride (3 mg/kg) resulted in a significant decrease below basal levels in plasma norepinephrine (NE) and epinephrine (EPI) that persisted following transfer and footshock whereas in saline-injected controls there were significant elevations in NE and EPI. In addition, chlorisondamine-treated rats were less active and deposited fewer fecal boli than did controls. In a second experiment, sham-operated and adrenal demedullated (A-D) rats received injections of saline or bretylium tosylate (a drug which blocks release of NE from sympathetic nerve endings). Administration of bretylium attenuated the increase in circulating levels of NE in rats following transfer to the shock chamber. In A-D rats, there was a reduction (> 90%) in plasma EPI throughout testing. Both bretylium and A-D significantly reduced increments in plasma levels of NE following 5 min of footshock. In addition, rats injected with bretylium were less active during footshock than were saline-injected rats. These results indicate that the adrenal medulla of rats is a significant source of circulating NE during mildly and intensely stressful stimulation (approximately 33 and 45%, respectively). Further, activity during footshock stress was greater in rats with an intact sympathetic nervous system. The presence of EPI in the circulation did not appear to have a significant effect on the activity of rats during stress. The possible mechanisms of alterations in behavior induced by peripheral catecholamines and the usefulness of bretylium in blocking sympathetic responses are discussed.

Sympatho-adrenal medullary activity and behavior during exposure to footshock stress: A comparison of seven rat strains

The effects of footshock stress on circulating levels of norepinephrine (NE) and epinephrine (EPI) and behavioral activation were examined in male rats of seven strains: spontaneously hypertensive (SHR), stroke-prone hypertensive (SP-SHR), Wistar-Kyoto (WKY), Sprague-Dawley (SD), Osborne-Mendel (OM), Brown Norway (BN), and Charles River Wistar (CRW). A catheter was inserted into the ventral caudal artery of each rat to allow for direct measurement of blood pressure and heart rate and for repeated sampling of blood in conscious, undisturbed animals. Two days after insertion of the catheter, resting levels of plasma NE and EPI were higher in SHRs than in CRWs; no other comparisons among strains were significant. No strain differences were noted in the increments in plasma NE and EPI following transfer of rats from the home cage to a shock chamber. There were, however, significant strain differences in the responses of rats to 5 min of footshock (2.5 mA, 0.4 sec duration every 5 sec). Shock-induced increments in plasma NE and EPI were greatest in SHRs and lowest in S-D, O-M, B-N and CRW strains. In addition, there was a significant positive relationship between activity and shock-induced increments in plasma NE (r=0.89, p<0.01) and EPI (r=0.93, p<0.01). These findings indicate an association between activity of the sympatho-adrenal medullary system and behavioral activation during footshock stress. In addition, responsivity to stress was greatest in those strains (SHR and SP-SHR) which are genetically predisposed to increases in blood pressure.