Diazepam attenuates the effects of cocaine on locomotion, 50-kHz ultrasonic vocalizations and phasic dopamine in the nucleus accumbens of rats.

Abstract

Currently, there is no effective drug to treat cocaine-use disorder, which affects millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine concentrations in the nucleus accumbens of rodents and block the increase in dopamine levels and appetitive 50-kHz ultrasonic vocalizations (USVs) induced by amphetamine in rats. Here, we tested whether administration of 2.5-mg·kg-1 diazepam (i.p.) in adult male rats could block the effects of 20-mg·kg-1 cocaine (i.p.) on electrically evoked phasic dopamine signals in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity. Cocaine injection increased evoked dopamine signals up to threefold within 5 min, and the increase was significantly higher than baseline for at least 75 min. The injection of diazepam, 5 min after cocaine, attenuated the cocaine effect by nearly 50%, and this attenuation was maintained for at least 40 min. Behaviourally, cocaine increased the number of appetitive 50-kHz calls by about 12-fold. Diazepam significantly blocked this effect for the entire duration of the session. Also, cocaine-treated rats were more active than controls and diazepam significantly attenuated cocaine-induced locomotion, by up to 50%. These results suggest that the neurochemical and psychostimulant effects of cocaine can be mitigated by diazepam. This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.