We examined whether a nicotinic receptor antagonist, mecamylamine (MEC) would affect escalation using the increased cocaine access-time procedure similar to the one described by Ahmed and colleagues. We found that when MEC was added to the cocaine solution that rats self-administered, escalation of intake did not occur (Figure 7; see also [69]). Moreover, we found that while MEC blocked the expression of increased cocaine self-administration, it may not have blocked its development because full escalation was observed the day after MEC was removed. These are exciting data because they show, first, that escalation of cocaine intake can be blocked without affecting normal (i.e. non-escalated) intake and, second, that neuroadaptations that underlie the development of increased cocaine-seeking behavior are independent of nicotinic receptors while those that are responsible for expression of higher drug-seeking require nicotinic receptor function.
