Stress and relapse to drug seeking in rats: studies on the generality of the effect.
BACKGROUND
Intermittent footshock reinstates drug-taking behavior in rats, but not behaviors previously maintained by food reinforcers. Here we tested further the generality of this phenomenon by determining whether restraint and food deprivation stressors would reinstate heroin seeking, whether the environment in which footshock is given modulates footshock-induced reinstatement, and whether footshock would reinstate operant responding previously maintained by brain stimulation reward (BSR).


METHODS
Groups of rats were trained to self-administer for 10 days either heroin (0.05-0.1 mg/kg/infusion, IV, three 3-h sessions/day) or brain stimulation into the septal area (trains of monopolar cathodal pulses of 100 micros for 500 ms, one 60-min session/day). After extinction of the heroin-reinforced behavior (10-13 days), the rats were tested for reinstatement after exposure to food deprivation (1 and 21 h), restraint given outside the self-administration environment (5, 15 and 30 min), or intermittent footshock (0.8 mA, 15 min) given in the self-administration environment or in a novel (non-drug) environment. For BSR-trained rats, the effect of footshock on reinstatement after extinction (6-10 days) was compared with that induced by noncontingent brain stimulation (three or six discrete stimulations at the start of the test sessions).


RESULTS
Food deprivation reinstated heroin seeking. Footshock reliably reinstated heroin seeking when given in the drug environment, but not when given in a non-drug environment. Similarly, restraint given outside the self-administration environment failed to reinstate heroin seeking. In addition, footshock was as effective as priming brain stimulation in reinstating operant responding previously maintained by BSR.


CONCLUSIONS
The effect of footshock on reinstatement of heroin seeking generalizes to food deprivation, and appears to be dependent on the environment in which the stressor is given. The data with BSR indicate that the phenomenon of footshock-induced reinstatement is not selective for drug reinforcers.
Shalev
U
U
Behavioral Neuroscience Branch, IRP/NIDA/NIH, Baltimore, MD 21224, USA.
Highfield
D
D
Yap
J
J
Shaham
Y
Y
D000818:Animals; D004558:Electric Stimulation; D004597:Electroshock; D005508:Food Deprivation; D003932:Heroin / Q000494:pharmacology; D006556:Heroin Dependence / Q000523:psychology; D008297:Male; D009294:Narcotics / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D012201:Reward; D020665:Septum of Brain / Q000502:physiology; D013315:Stress, Psychological / Q000523:psychology*; D019966:Substance-Related Disorders / Q000523:psychology*
D009294:Narcotics; D003932:Heroin