Time-dependant effects of systemic muscimol on extinction (EXT) of a conditioned taste aversion (CTA)

GABA (γ-aminobutyric acid) receptor manipulation has been proposed as an important mediator of extinction (EXT). The current experiments paired 0.3 % saccharin (SAC) with 81 mg/kg Lithium Chloride (LiCl; i.p.) to establish a strong CTA in adult, male Sprague-Dawley rats. During extinction, subsequent opportunities to drink SAC were either preceded, or followed, by an injection of the GABA agonist muscimol (1.0 mg/kg, i.p.). Muscimol given 0.75 hr after SAC exposure significantly impaired EXT learning in rats compared to rats that received muscimol 0.5 hr before SAC exposure. The days required to reach asymptotic EXT did not differ between rats that received muscimol before daily SAC drinking and those that received no muscimol. A second study tested the hypothesis that muscimol given after CS exposure can act as a US and cause a CTA. This experiment paired rat SAC drinking with muscimol (1.0 mg/kg, i.p.), instead of LiCl. Each subsequent exposure to SAC during the acquisition phase resulted in approximately the same consumption of SAC as on the first day of exposure. Thus, these rats neither developed a strong aversion nor did they overcome the initial neophobia (natural avoidance of a novel taste) and readily accept the SAC. These data suggest that the GABA agonist muscimol can impair EXT of a CTA but this phenomenon depends on the timing of the drug administration relative to CS re-exposures. The exact mechanism by which muscimol retards EXT is currently unknown. The drug may be, (a) acting as a weak US, (b) impairing sensory processing of the SAC taste, (c) blocking the taste memory itself, or (d) having direct effects on EXT memory formation. Continuing studies are addressing these possibilities