Recent Advances on GABAB Receptor Positive Allosteric Modulators as Potential Pharmacotherapies for Substance Use Disorder and Food Addiction

Υ-aminobutyric acid (GABA) type-B (GABAB) receptors and their positive allosteric modulators (PAMs) are indicated as potential pharmacological tools for use in the treatment of a series of brain disorders, including substance use disorder (SUD). This chapter describes the current state of preclinical findings on (i) the interaction of drugs of abuse and GABAB receptors in the brain and signaling pathways and (ii) the effects of GABAB PAMs in several behavioral paradigms relating to reward, motivation, and seeking behaviors. Data obtained in recent years has indicated that GABAB PAMs may exert therapeutic efficacy in the context of addiction to psychostimulants (amphetamines and cocaine), nicotine, and opioids. Several GABAB PAMs also displayed efficacy in reducing food-maintaining behaviors; however, further investigations should be conducted to assess whether this pharmacological approach represents a primary mechanism and may be of use in the treatment of food addiction or eating disorders. Behavioral profiling of GABAB PAMs indicates a resemblance to the clinically approved drug baclofen, an orthosteric GABAB receptor agonist. As GABAB PAMs display a better side-effect profile compared to GABAB receptor orthosteric agonists, they may be of significant use in targeting specific brain regions and processes associated with drug or food reward, seeking, and withdrawal.