GABAergic attenuation of cocaine-induced dopamine release and locomotor activity

Abstract

GABA modulates dopamine concentrations in the nucleus accumbens and corpus striatum. Using in vivo microdialysis techniques we examined this modulatory role and the extent to which three different GABAergic drugs can attenuate cocaine's ability to increase extracellular dopamine concentrations and gross locomotor activity. Ethanol, lorazepam (Ativan), and gamma-vinyl GABA (GVG) significantly and dose-dependently attenuated cocaine-induced dopamine release in the corpus striatum of freely moving animals. Unlike ethanol or lorazepam, however, GVG is not a sedative hypnotic in the doses used, and hence the strategy of selectively increasing GABAergic activity by suicide inhibition of the catabolic enzyme, GABA-transaminase, offers the unique advantage of attenuating cocaine-induced dopamine release without the apparent side effects typically associated with sedative hypnotics.

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

“…Previously, we reported that diazepam blocked 50‐kHz calls elicited by amphetamine (de Oliveira Guaita et al, 2018), but to our knowledge, the present study is the first to report that diazepam also blocked the 50‐kHz calls elicited by cocaine. The present work also confirms previous findings (Augier et al, 2012; Delfs et al, 1990; Dewey et al, 1997; Kiyatkin & Bae, 2008; Maier et al, 2010) that diazepam attenuates the locomotor stimulant effect of cocaine that is associated with cocaine amplification of extracellular dopamine concentrations in the dorsal and ventral striatum.…”

Tiagabine increases cocaine‐free urines in cocaine‐dependent methadone‐treated patients: results of a randomized pilot study

“…These results are consistent with pre‐clinical trials that examined the efficacy of similar GABAergic medications on cocaine effects in rodents and primates (Dewey et al . 1997; Dewey et al .…”

Age-dependent effects of κ-opioid receptor stimulation on cocaine-induced stereotyped behaviors and dopamine overflow in the caudate–putamen: an in vivo microdialysis study

“…In adult rats, cocaine (25 mg/kg, IP) increased dopamine dialysate levels in the dorsal CPu by as much as 245%, which is consistent with typical lower-end literature values (e.g., Chen et al, 1996; Martin-Fardon et al, 1996; Dewey et al, 1997; Kreuter et al, 2004). Importantly, this cocaine-induced increase in dopamine overflow was completely attenuated by a pretreatment injection of U50,488 (5 mg/kg, IP).…”