Operant ethanol self-administration after nicotine treatment and withdrawal.

The effects of chronic intermittent administration of nicotine (NIC) and withdrawal on operant ethanol (EtOH) self-administration were tested in Long-Evans rats (n = 8). EtOH self-administration (10% v/v, Fixed Ratio 4 reinforcement schedule) was induced by the sucrose-substitution procedure. Then the animals were divided into two groups of four rats matched on EtOH self-administration and the locomotor activity following an injection of NIC (0.35 mg/kg, SC) or saline was measured. The groups then received 9 days of injection of either NIC (0.35 mg/kg) or saline and then motor activity was retested using the initial NIC dose. This was followed by 17 days of NIC injections (0.6 mg/kg) or saline injections. A final locomotor test using the higher NIC dose was then conducted. The initial acute administration of NIC had no effect on motor activity compared to saline (measured by the number of horizontal movements). However, after the repeated treatment, the group of animals injected chronically and acutely with NIC showed motor activation in comparison with the animals injected chronically with saline and injected acutely with NIC only on the days of activity testing. At the end of the chronic NIC treatment, operant EtOH self-administration was not changed. However, 6 days after the NIC injections were concluded, a change in the pattern of responding for EtOH was observed in the NIC group, showing a decrease in the mean rate of responding during the first half of the operant self-administration session. When both groups were again tested for locomotor activity at the end of the operant self-administration experiment, the increased motor activity in the NIC group was still observed. The results suggest that alterations in the nicotinic system may affect EtOH self-administration, but this appears to be only modulatory, even with a significant change in locomotor response to NIC following chronic NIC administration.