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

Brain Res. 2010 Aug 12:1348:84-94. doi: 10.1016/j.brainres.2010.06.029. Epub 2010 Jun 17.

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) (100nM, 1microl/hemisphere) or vehicle (0.15M NaCl) into the amygdala either 5min prior to, or 5min after, a single pairing of sodium saccharin (0.125%, 10-min access) and LiCl or NaCl (0.15M, 3ml/kg i.p.). Two-bottle, 24-h preference tests were conducted for 13days 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 13days. 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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Amygdala / drug effects*
  • Animals
  • Avoidance Learning / drug effects*
  • Behavior, Animal / drug effects
  • CREB-Binding Protein / metabolism*
  • Conditioning, Classical / drug effects
  • Food Preferences / drug effects
  • Lithium Chloride / administration & dosage
  • Male
  • Okadaic Acid / pharmacology*
  • Phosphorylation / drug effects
  • Rats
  • Rats, Sprague-Dawley
  • Saccharin / administration & dosage
  • Statistics, Nonparametric
  • Sweetening Agents / administration & dosage
  • Taste / drug effects*

Substances

  • Sweetening Agents
  • Okadaic Acid
  • CREB-Binding Protein
  • Saccharin
  • Lithium Chloride