Test

Pretreatment CPP Saline

Pretreatment CPP Saline

NAME Saline

NAME Saline

Fig. 8. Effects of CPP, MK-801 and NAME on the expression of cocaine-induced conditioned increases in locomotor activity. (A) Effects of saline pretreatment during the test day on expression following injection of saline; (B) effects of CPP pretreatment (20 mg/kg ip) during the test day on expression following injections of saline; (C) Effects of MK-801 (0.25 ng/kg ip) pretreatment during the test day on expression; (D) effects of NAME pretreatment during the test day on expression. *p < 0.05 for comparisons between PAIRED and UNPAIRED rats on the test day with the Scheffe test for post hoc comparisons. All values are means + SEM.

Fig. 9. Effects of test-day CPP pretreatment on the expression of cocaine-induced conditioned increases in locomotor activity following one conditioning session. *p < 0.05 for comparisons between PAIRED and UNPAIRED rats on the test day with the Scheffe test for post hoc comparisons. All values are means ± SEM.

Fig. 9. Effects of test-day CPP pretreatment on the expression of cocaine-induced conditioned increases in locomotor activity following one conditioning session. *p < 0.05 for comparisons between PAIRED and UNPAIRED rats on the test day with the Scheffe test for post hoc comparisons. All values are means ± SEM.

injected with 10 mg/kg of cocaine and then run for 30 min in the activity chambers. Neither dose of CPP prevented the expression of cocaine-conditioned effects (Fig. 9).

The VTA appears to be the principal brain region involved in the acquisition of cocaine-conditioned increases in locomotor activity as well as context-independent sensitization. The purpose of the next study was to determine whether direct blockade of NMDA receptor function in the VTA would prevent the expression of cocaine-conditioned behavior. Rats were implanted with bilateral cannulae guides aimed for an area 2 mm dorsal to the VTA. Two weeks later, the animals were divided into two groups (PAIRED and UNPAIRED). Animals in each group were treated for 3 d with 30 mg/kg of cocaine, as described above. On d 4, one-half of the PAIRED and UNPAIRED rats were injected bilaterally in the VTA with 5 nmol of MK-801 in 1 ||L of aCSF and the other half were injected with the vehicle. Immediately after the intracerebral injections, all rats were injected intraperitoneally with saline and then placed in locomotor chambers for 30 min. Although MK-801 injections into the VTA increased locomotor activity in both the PAIRED and UNPAIRED rats, it failed to eliminate the expression of the conditioned response (Fig. 10).

Although intact NMDA receptor function does not appear to be critical for the expression of sensi-tization, whether context dependent or context independent, there is evidence that the AMPA subtype of glutamate receptors might be involved (25,54). The ability of DNQX, a relatively selective antagonist of the AMPA receptor, to alter the expression fo cocaine-conditioned increases in locomotor activity was evaluated by the injection of 25 nmol of this antagonist icv prior to the test for conditioning 1 d following three conditioning sessions. DNQX was found to fully prevent the expression of cocaine-induced conditioned effects, even though it had little effect on locomotor activity by itself (Fig. 11). These findings are similar to those reported by Cervo and Samanin (54).

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