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

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 15 min-sessions. The treatment with biperiden (doses of 0.1, 1 and 10 mg/kg) was made 30 min prior to the testing session. For behavioral sensitization development, cocaine was administered at the dose of 10 mg/kg for 10 days. After sensitization, two challenges were performed: saline and cocaine (5 mg/kg). Biperiden (10 mg/kg) was administered 30 min before the cocaine challenge. At the dose of 10 mg/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.

Behavioral effects induced by subchronic exposure to Pb and their reversion are concentration and gender dependent.

Lead (Pb) seems to be involved in the etiology of psychological pathologies. This study investigated the effects of subchronic Pb exposure from weaning to adulthood on anxiety, depression and aggressiveness in male and female Swiss mice. Moreover, the reversibility of the effects was evaluated retesting the animals 30 days after the end of exposure. Swiss male and female mice (21 days) were exposed to 0, 50, 100 or 500 ppm of Pb, as Pb acetate, in drinking water for 70 days and were submitted to the forced swimming, tail suspension, elevated plus-maze or intruder-resident tests. Pb exposure to 50 and 500 ppm induced anti-depressant-like effect in both males and females, whereas exposure to 500 ppm induced anxiogenic effect only in males. Interruption of exposure was able to reverse the behavioral alterations in females, but not in males exposed to the highest concentration (500 ppm). Our results suggest that behavioral effects induced by subchronic exposure to Pb from weaning to adulthood and their reversion are concentration and gender dependent.