Repeated as well as an acute exposure to psychostimulants like cocaine is characterized by enhanced neurochemical and behavioral responses to a subsequent administration of the same drug (sensitization). This phenomenon is associated not only with the dopaminergic mesocorticolimbic system, but also with other neurotransmitters systems, such as methionine-enkephalin (met-ENK). We previously demonstrated that acute and chronic administration of amphetamine or cocaine induce both an increase in met-ENK levels in key mesocorticolimbic brain areas, such as nucleus accumbens and prefrontal cortex, which suggest the involvement of the enkephalinergic system in the sensitization to psychostimulants. Thus, we studied the development of behavioural sensitization to cocaine in wild type (Penk +/+) and knockout (Penk -/-) preproenkephalin mice. Penk +/+ and Penk -/- male C57B/6J mice were treated with a daily saline or cocaine (15mg/Kg/day, ip) injection during 9 days, and were exposed to a challenge cocaine dose (7.5mg/kg, ip) on day 15 and 21. The locomotor activity was recorded 30 min after each injection. The acute locomotor response to cocaine was similar in wild type (Penk +/+) and knockout (Penk -/-). However, the behavioral sensitization to cocaine was not evidenced in the knockout mice as compared with their wild type controls. This finding is the first one showing the involvement of the enkephalinergic system in the cocaine-induced behavioral sensitization.
