A key goal was to identify whether inactivation of cholinergic input to VTA can reduce expression of escalated cocaine intake. In a recent study, we found that microinjection of the nAChR antagonist mecamylamine (60 µg/side) reduced escalated cocaine intake (Figure 8) but did not reduce cocaine intake below pre-escalation levels. Rats self-administered cocaine for 1 hr per day in the pre-escalation phase. The average level of cocaine intake in 1 hr access sessions is represented by the dotted line. Rats were then given 6 hr per day access and cocaine intake increased. Microinjections of MEC were given between 8–12 days after the beginning of the 6 hr access sessions. Results are expressed as a percentage of pre-injection baseline, which was the average of the last 2 days of cocaine infusions on the 6 hr access schedule. At a concentration of 60 µg/side, intra-VTA injection of mecamylamine significantly reduced escalated intake but did not reduce cocaine self-administration below pre-escalation levels. As a control, we injected the GABAB agonist baclofen to confirm that intra-VTA injections of a drug known to reduce non-escalated cocaine intake would be effective at reducing cocaine intake below the pre-escalation baseline.
