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The Journal of Neuroscience, August 23, 2006, 26(34):8800-8803; doi:10.1523/JNEUROSCI.2076-06.2006

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Brief Communications
GABA_B(1) Receptor Isoforms Differentially Mediate the Acquisition and Extinction of Aversive Taste Memories

Laura H. Jacobson,¹ Peter H. Kelly,¹ Bernhard Bettler,² Klemens Kaupmann,¹ and John F. Cryan^1,3

¹Novartis Institutes for BioMedical Research, Novartis Pharma, CH-4002 Basel, Switzerland, ²Institute of Physiology, Department of Clinical-Biological Sciences, Pharmazentrum, University of Basel, CH-4056 Basel, Switzerland, and ³Department of Pharmacology and Therapeutics, School of Pharmacy, University College Cork, Cork, Ireland

Correspondence should be addressed to Dr. John F. Cryan at his present address: Department of Pharmacology and Therapeutics, School of Pharmacy, University College Cork, Cork, Ireland. Email: j.cryan{at}ucc.ie

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.

Key words: conditioned taste aversion; GABA_B; anxiety; inhibitory; learning; extinction

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Received May 16, 2006; revised June 28, 2006; accepted July 11, 2006.

Correspondence should be addressed to Dr. John F. Cryan at his present address: Department of Pharmacology and Therapeutics, School of Pharmacy, University College Cork, Cork, Ireland. Email: j.cryan{at}ucc.ie

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