Preexposure to foot-shock sensitizes the locomotor response to subsequent systemic morphine and intra-nucleus accumbens amphetamine.

The effect of repeated exposure to foot-shock on locomotor activity was examined by testing rats in the shock boxes for one hour following shock exposure. Early in testing activity was elevated relative to the nonshocked control group, between 40-60 min following shock. Over days this period of elevated activity occurred sooner in time and lengthened in duration. When these animals were tested in the absence of shock, those preexposed to shock were more active following either saline or morphine (0.5 and 5.0 mg/kg IP) injections. In a second experiment, elevated spontaneous and morphine-induced activity was also found when rats had been preexposed to shock in boxes distinct from the activity test boxes. In a final experiment, animals preexposed to shock were tested after bilateral infusions of either amphetamine (5 and 10 micrograms/microliters/side) or morphine (5 micrograms/microliters/side) into the nucleus accumbens (NAS). On the amphetamine tests, previously shocked animals were significantly more active than control animals. In contrast, intra-NAS infusions of morphine failed to differentiate between the two groups. These results suggest that repeated mild foot-shock sensitizes the mesolimbic dopamine system by mechanisms similar to those mediating the sensitized behavioral and dopaminergic responses seen following repeated opioid or stimulant administration.