Dissociation of psychomotor sensitization from compulsive cocaine consumption.

Ahmed SH, Cador M.

The transition from drug use to drug addiction is associated with a process of
escalation, whereby drug use becomes excessive and difficult to control. Several
mechanisms have been advanced to explain escalating patterns of drug use as
opposed to nonescalating patterns. Although current evidence favors hedonic
tolerance, there remains some dispute about the contribution of behavioral
sensitization to cocaine intake escalation. Here, we concurrently assessed the
ability of cocaine to induce psychomotor sensitization and drug-seeking behavior
in animals with 1-h (short access or ShA) vs 6-h (long access or LgA) access to
intravenous (i.v.) cocaine self-administration. As expected, cocaine intake by
LgA rats escalated over time and became excessive compared to cocaine intake by
ShA rats, which remained low and stable. Despite escalated levels of cocaine
consumption, however, LgA rats were not more sensitized to cocaine than ShA rats.
The dose-effect function for cocaine-induced locomotion (0.125-1 mg, i.v.) was
shifted to the left in LgA rats by the same amount as in ShA rats after cocaine
self-administration. In contrast, LgA rats were much more responsive than ShA
rats to the motivational effects of cocaine, as measured by the ability of i.v.
cocaine to reinstate extinguished drug-seeking behavior. This study demonstrates
a dissociation of psychomotor sensitization from the change in motivation
underlying the transition to compulsive cocaine consumption, and therefore
suggests that responsiveness to the motivational effects of the drug, not
psychomotor sensitization, would represent a specific behavioral marker of the
transition to and maintenance of compulsive cocaine use.

DOI: 10.1038/sj.npp.1300834
PMID: 16034440 [Indexed for MEDLINE]

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