GABA(B(1)) receptor isoforms differentially mediate the acquisition and extinction of aversive taste memories.
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Jacobson, Laura, Kelly, Peter, Bettler, Bernhard, Kaupmann, Klemens and Cryan, John F. (2006) GABA(B(1)) receptor isoforms differentially mediate the acquisition and extinction of aversive taste memories. The Journal of Neuroscience : the official journal of the Society for Neuroscience, 26 (34). pp. 8800-8803. ISSN 1529-2401
Abstract
Conditioned taste aversion (CTA) is a form of aversive memory in which an association is made between a consumed substance and a subsequent malaise. CTA is a critical mechanism for the successful survival, and hence evolution, of most animal species. The role of excitatory neurotransmitters in the neurochemical mechanisms of CTA is well recognized; however, less is known about the involvement of inhibitory receptor systems. In particular, the potential functions of metabotropic GABA(B) receptors in CTA have not yet been fully explored. GABA(B) receptors are metabotropic GABA receptors that are comprised of two subunits, GABA(B(1)) and GABA(B(2)), which form heterodimers. The Gabbr1 gene is transcribed into two predominant isoforms, GABA(B(1a)) and GABA(B(1b)), which differ in sequence primarily by the inclusion of a pair of sushi domains (also known as short consensus repeats) in the GABA(B(1a)) N terminus. The behavioral function of mammalian GABA(B(1)) receptor isoforms is currently unknown. Here, using a point mutation strategy in mice, we demonstrate that these two GABA(B(1)) receptor isoforms are differentially involved in critical components of CTA. In contrast to GABA(B(1b))-/- and wild-type mice, GABA(B(1a))-/- mice failed to acquire CTA. In contrast, GABA(B(1b))-/- mice robustly acquired CTA but failed to show any extinction of this aversion. The data demonstrate that GABA(B) receptors are involved in both the acquisition and extinction of CTA; however, receptors containing the GABA(B(1a)) or the GABA(B(1b)) isoform differentially contribute to the mechanisms used to learn and remember the salience of aversive stimuli.
| Item Type: | Article |
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| Additional Information: | author can archive post-print (ie final draft post-refereeing), On author's personal web site and institutional repository |
| Keywords: | conditioned taste aversion; GABAB; anxiety; inhibitory; learning; extinction |
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| Date Deposited: | 14 Dec 2009 13:57 |
| Last Modified: | 31 Jan 2013 01:12 |
| URI: | https://oak.novartis.com/id/eprint/607 |