Baclofen administration alters fear extinction and GABAergic protein levels

The investigation of GABAergic systems in learning and extinction has principally focused on ionotropic GABAA receptors. Less well characterized is the metabotropic GABAB receptor, which when activated, induces a more sustained inhibitory effect and has been implicated in regulating oscillatory activity. Few studies have been carried out utilizing GABAB ligands in learning, and investigations of GABAB in extinction have primarily focused on interactions with drugs of abuse. The current study examined changes in GABAB receptor function using the GABAB agonist baclofen (2 mg/mL) or the GABAB antagonist phaclofen (0.3 mg/mL) on trace cued and contextual fear conditioning and extinction. The compounds were either administered during training and throughout extinction in Experiment 1, or starting 24 h after training and throughout extinction in Experiment 2. All drugs were administered 1 mL/kg via intraperitoneal injection. These studies demonstrated that the administration of baclofen during training and extinction trials impaired animals’ ability to extinguish the fear association to the CS, whereas the animals that were administered baclofen starting 24 h after training (Experiment 2) did display some extinction. Further, contextual fear extinction was impaired by baclofen in both experiments. Tissue analyses suggest the cued fear extinction deficit may be related to changes in the GABAB2 receptor subunit in the amygdala. The data in the present investigation demonstrate that GABAB receptors play an important role in trace cued and contextual fear extinction, and may function differently than GABAA receptors in learning, memory, and extinction.

► Baclofen administered during training impaired extinction to the CS.
► Regardless of time of administration, baclofen impaired contextual extinction.
► GABAB2 subunit in amygdala may mediate extinction to the CS.