Intra-amygdalar okadaic acid enhances conditioned taste aversion learning and CREB phosphorylation in rats

Abstract

Protein phosphatases (PPs) regulate many substrates implicated in learning and memory. Conditioned taste aversion (CTA) learning, in which animals associate a novel taste paired with a toxin and subsequently avoid the taste, is dependent on several serine/threonine phosphatase substrates and the PP1-binding protein spinophilin. In order to examine the effects of PP1/2A blockade on CTA acquisition and extinction, rats received bilateral infusions of okadaic acid (OA) (100 nM, 1 μl/hemisphere) or vehicle (0.15 M NaCl) into the amygdala either 5 min prior to, or 5 min after, a single pairing of sodium saccharin (0.125%, 10-min access) and LiCl or NaCl (0.15 M, 3 ml/kg i.p.). Two-bottle, 24-h preference tests were conducted for 13 days to measure CTA expression and extinction. Rats conditioned with saccharin and LiCl showed a decreased preference for saccharin, and OA administered before (but not after) the pairing of saccharin and LiCl resulted in a significantly stronger CTA that did not extinguish over 13 days. The enhancement of the CTA was not due to aversive effects of OA, because rats given OA and a pairing of saccharin and NaCl did not acquire a CTA. Finally, OA administration increased levels of phosphorylated CREB immunoreactivity following a CTA trial. Together, these results suggest a critical role for PP1/2A during normal CTA learning. Because CTA learning was enhanced only when OA was given prior to conditioning, phosphatase activity may be a constraint on learning during the taste-toxin interval but not during acquisition and consolidation processes that occur after toxin administration.