GABAB receptors as a therapeutic strategy in substance use disorders: Focus on positive allosteric modulators

Psychostimulants

“…Among three subtypes of GABA receptors, accumulating data over the past decades clearly supports a role of GABA B receptors in mediating longterm neuroplastic changes which are the consequences of SUD-like behavior (Filip & Frankowska, 2008;Filip et al, 2015).…”

“…Such drugs have the advantage over classical agonists, like baclofen, that desensitization will not be observed following continued treatment and have fewer side effects, such as myorelaxation, hyperthermia, and cognitive dysfunction (Filip et al, 2015). Evidence suggests that the GABA B -positive allosteric modulators abrogate ethanol, cocaine, or nicotine-induced locomotor activity in mice, did not reduce the expression of cocaine or ethanol sensitization, while there was reduction in the development of cocaine sensitization.…”

Repurposing established cyclic adenosine monophosphate reducing agents for the prevention and therapy of epidermal growth factor receptor inhibitor resistance in non-small cell lung cancer

“…Positive allosteric modulators (PAMs) of G i -coupled receptors circumvent this problem as they do not change receptor sensitivity. PAMs for the GABA B -Receptor are currently used for the treatment of drug addiction (22) while PAMs for opioid receptors are currently being developed (23).…”

Behavioural endophenotypes in mice lacking the auxiliary GABAB receptor subunit KCTD16

“…In addition, GABA B receptor antagonists showed anxiolytic and antidepressant-like activity in a number of animal models [15][16][17][18][19]. Accordingly, GABA B receptors have been proposed as a potential treatment target for these major neuropsychiatric disorders as well as for anxiety disorders and addiction [20][21][22][23]. The KCTD proteins are also associated with neuropsychiatric disorders.…”