Biperiden (M1 antagonist) impairs the expression of cocaine conditioned place preference but potentiates the expression of cocaine-induced behavioral sensitization

Abstract

Cocaine addiction is a public health issue in many countries, stressing the need for more effective treatments. As all drugs of abuse, cocaine acts on the brain reward system, increasing dopamine (DA) levels. Other neurotransmitters such as acetylcholine (ACh) are involved in the mechanisms underlying the development and the maintenance of cocaine addiction. ACh plays an important role in learning and memory processes and also regulates DA in some specific regions of the central nervous system. The present study investigated the effects of biperiden, a muscarinic cholinergic (mACh) antagonist in two animal models: conditioned place preference (CPP) and behavioral sensitization. Male C57BL/6J mice were used in both studies. The CPP protocol was unbiased and carried out in three phases: habituation, conditioning and testing. For conditioning, cocaine was injected at a dose of 10mg/kg in eight 15min-sessions. The treatment with biperiden (doses of 0.1, 1 and 10mg/kg) was made 30min prior to the testing session. For behavioral sensitization development, cocaine was administered at the dose of 10mg/kg for 10 days. After sensitization, two challenges were performed: saline and cocaine (5mg/kg). Biperiden (10mg/kg) was administered 30min before the cocaine challenge. At the dose of 10mg/kg, biperiden blocked the cocaine-CPP expression, suggesting an effect on conditioned memory retrieval. However, the same dose potentiated the expression of behavioral sensitization, suggesting an increase in DA release, probably in the NAc. Biperiden, as other mACh antagonists, may be a promising drug for the pharmacologic treatment of cocaine addiction.