QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, May 19, 2004, 24(20):4723-4727; doi:10.1523/JNEUROSCI.0176-04.2004

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (70) Citing Articles via Google Scholar Google Scholar Articles by Baptista, M. A. S. Articles by Weiss, F. Search for Related Content PubMed PubMed Citation Articles by Baptista, M. A. S. Articles by Weiss, F.

 Previous Article  |  Next Article 

BRIEF COMMUNICATION
Preferential Effects of the Metabotropic Glutamate 2/3 Receptor Agonist LY379268 on Conditioned Reinstatement versus Primary Reinforcement: Comparison between Cocaine and a Potent Conventional Reinforcer

Marco A. S. Baptista, Rémi Martin-Fardon, and Friedbert Weiss

Department of Neuropharmacology, The Scripps Research Institute, La Jolla, California 92037

Metabotropic glutamate receptors (mGluRs) have been implicated in regulating anxiety, stress responses, and the neurobehavioral effects of psychostimulants. The present study sought to determine whether group II mGluR activation by the potent mGlu2/3 receptor agonist, (–)-2-oxa-4-aminobicylco hexane-4,6-dicarboxylic acid (LY379268), antagonizes reinstatement of cocaine-seeking induced by cocaine-related stimuli and whether this effect extends to behavior induced by stimuli conditioned to a potent conventional reinforcer, sweetened condensed milk (SCM). Also, we tested whether the suppressant effects of LY379268 on conditioned reinstatement extend to the primary reinforcing effects of cocaine or SCM. Rats were trained to associate discriminative stimuli (S^D) with the availability of cocaine or SCM versus non-reward and then subjected to repeated extinction sessions during which the respective reinforcers and S^D were withheld. Subsequent reexposure to the cocaine or SCM S^D, but not the non-reward S^D, produced recovery of responding at the previously active lever. LY379268 (0.3–3.0 mg/kg, s.c.) dose-dependently attenuated recovery of cocaine seeking but reduced conditioned reinstatement by the SCM S^D only at the highest dose. LY379268 did not alter responding reinforced directly by SCM, and only the highest LY379268 dose reduced cocaine self-administration. The results suggest that the effects of LY379268 are selective for behavior maintained by cocaine as opposed to palatable conventional reinforcers. More importantly, the results show that LY379268 suppresses behavior motivated by stimuli conditioned to cocaine or SCM more effectively than consummatory behavior maintained by the unconditioned effects of these substances. As such, the results identify group II mGluRs as a pharmacotherapeutic target for craving and relapse prevention associated with cocaine cue exposure.

Key words: addiction; self-administration; drug-seeking behavior; relapse; drug cues; group II mGluRs

---

Received Jan 16, 2004; revised March 25, 2004; accepted April 12, 2004.

This article has been cited by other articles:

				R. Martin-Fardon, M. A. S. Baptista, C. V. Dayas, and F. Weiss Dissociation of the Effects of MTEP [3-[(2-Methyl-1,3-thiazol-4-yl)ethynyl]piperidine] on Conditioned Reinstatement and Reinforcement: Comparison between Cocaine and a Conventional Reinforcer J. Pharmacol. Exp. Ther., June 1, 2009; 329(3): 1084 - 1090. [Abstract] [Full Text] [PDF]

				J. Peters, P. W. Kalivas, and G. J. Quirk Extinction circuits for fear and addiction overlap in prefrontal cortex Learn. Mem., April 20, 2009; 16(5): 279 - 288. [Abstract] [Full Text] [PDF]

				A. Madayag, D. Lobner, K. S. Kau, J. R. Mantsch, O. Abdulhameed, M. Hearing, M. D. Grier, and D. A. Baker Repeated N-Acetylcysteine Administration Alters Plasticity-Dependent Effects of Cocaine J. Neurosci., December 19, 2007; 27(51): 13968 - 13976. [Abstract] [Full Text] [PDF]

				U. E. Ghitza, S. G. Nair, S. A. Golden, S. M. Gray, J. L. Uejima, J. M. Bossert, and Y. Shaham Peptide YY3-36 Decreases Reinstatement of High-Fat Food Seeking during Dieting in a Rat Relapse Model J. Neurosci., October 24, 2007; 27(43): 11522 - 11532. [Abstract] [Full Text] [PDF]

				M. E. Liechti, L. Lhuillier, K. Kaupmann, and A. Markou Metabotropic Glutamate 2/3 Receptors in the Ventral Tegmental Area and the Nucleus Accumbens Shell Are Involved in Behaviors Relating to Nicotine Dependence J. Neurosci., August 22, 2007; 27(34): 9077 - 9085. [Abstract] [Full Text] [PDF]

				L. M. Rorick-Kehn, B. G. Johnson, J. L. Burkey, R. A. Wright, D. O. Calligaro, G. J. Marek, E. S. Nisenbaum, J. T. Catlow, A. E. Kingston, D. D. Giera, et al. Pharmacological and Pharmacokinetic Properties of a Structurally Novel, Potent, and Selective Metabotropic Glutamate 2/3 Receptor Agonist: In Vitro Characterization of Agonist (-)-(1R,4S,5S,6S)-4-Amino-2-sulfonylbicyclo[3.1.0]-hexane-4,6-dicarboxylic Acid (LY404039) J. Pharmacol. Exp. Ther., April 1, 2007; 321(1): 308 - 317. [Abstract] [Full Text] [PDF]

				P. W. Kalivas and N. D. Volkow The Neural Basis of Addiction: A Pathology of Motivation and Choice Focus, January 1, 2007; 5(2): 208 - 219. [Abstract] [Full Text] [PDF]

				Y. Zhao, C. V. Dayas, H. Aujla, M. A. S. Baptista, R. Martin-Fardon, and F. Weiss Activation of Group II Metabotropic Glutamate Receptors Attenuates Both Stress and Cue-Induced Ethanol-Seeking and Modulates c-fos Expression in the Hippocampus and Amygdala J. Neurosci., September 27, 2006; 26(39): 9967 - 9974. [Abstract] [Full Text] [PDF]

				Z.-X. Xi, J. G. Gilbert, X.-Q. Peng, A. C. Pak, X. Li, and E. L. Gardner Cannabinoid CB1 Receptor Antagonist AM251 Inhibits Cocaine-Primed Relapse in Rats: Role of Glutamate in the Nucleus Accumbens. J. Neurosci., August 15, 2006; 26(33): 8531 - 8536. [Abstract] [Full Text] [PDF]

				A. S. Adewale, D. M. Platt, and R. D. Spealman Pharmacological Stimulation of Group II Metabotropic Glutamate Receptors Reduces Cocaine Self-Administration and Cocaine-Induced Reinstatement of Drug Seeking in Squirrel Monkeys J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 922 - 931. [Abstract] [Full Text] [PDF]

				L. M. Rorick-Kehn, E. J. Perkins, K. M. Knitowski, J. C. Hart, B. G. Johnson, D. D. Schoepp, and D. L. McKinzie Improved Bioavailability of the mGlu2/3 Receptor Agonist LY354740 Using a Prodrug Strategy: In Vivo Pharmacology of LY544344 J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 905 - 913. [Abstract] [Full Text] [PDF]

				P. W. Kalivas and N. D. Volkow The Neural Basis of Addiction: A Pathology of Motivation and Choice Am J Psychiatry, August 1, 2005; 162(8): 1403 - 1413. [Abstract] [Full Text] [PDF]

				M. M. Moran, K. McFarland, R. I. Melendez, P. W. Kalivas, and J. K. Seamans Cystine/Glutamate Exchange Regulates Metabotropic Glutamate Receptor Presynaptic Inhibition of Excitatory Transmission and Vulnerability to Cocaine Seeking J. Neurosci., July 6, 2005; 25(27): 6389 - 6393. [Abstract] [Full Text] [PDF]

				J. M. Bossert, S. Y. Liu, L. Lu, and Y. Shaham A Role of Ventral Tegmental Area Glutamate in Contextual Cue-Induced Relapse to Heroin Seeking J. Neurosci., November 24, 2004; 24(47): 10726 - 10730. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help