The Group II Metabotropic Glutamate Receptor Agonist, LY379268, Inhibits Both Cocaine- and Food-seeking Behavior in Rats

Overview

Journal Psychopharmacology (Berl)

Specialty Pharmacology

Date 2006 May 17

PMID 16703399

Citations 109

Authors

Jamie Peters

Peter W Kalivas

Affiliations

Soon will be listed here.

Abstract

Rationale: Group II metabotropic glutamate receptor (mGluR2/3) agonists are proposed to serve as potential treatment for addiction.

Objectives: The present study examined the hypothesis that mGluR2/3 agonists exert inhibitory effects on cocaine-induced reinstatement of cocaine-seeking.

Methods: Rats were trained to self-administer either cocaine or control reinforcer (food), then responding on the reinforcer-paired lever was extinguished. Reinstatement of responding was induced by a noncontingent presentation of the self-administered reinforcer (10 mg/kg cocaine, i.p. or 765 mg of food). In one experiment, rats were systemically pretreated with vehicle (Veh) or the mGluR2/3 agonist LY379268 (0.3, 1, or 3 mg/kg, i.p.) 30 min before the reinstatement test session. In a second experiment, Veh or LY379268 (0.05, 0.5, or 5 nmol/side) was microinjected into the nucleus accumbens core (NAc core) 5 min before the reinstatement test session. The effects of LY379268 on cocaine- and food-induced reinstatement on reward seeking were assessed.

Results: Both systemic and intra-NAc core pretreatment with LY379268 inhibited both cocaine- and food-seeking behavior. However, the effect of LY379268 appeared somewhat more effective for cocaine-seeking than food-seeking.

Conclusions: These results support a potential therapeutic role for mGluR2/3 agonists on relapse of cocaine-seeking. However, doses that inhibited cocaine-seeking were only threefold lower than those inhibiting food-seeking, indicating possible unacceptable nonspecific effects. In addition, the NAc core is one site of action where the mGluR2/3 agonists elicit effects on reward-seeking behavior.

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References

Lujan R, Roberts J, Shigemoto R, Ohishi H, Somogyi P . Differential plasma membrane distribution of metabotropic glutamate receptors mGluR1 alpha, mGluR2 and mGluR5, relative to neurotransmitter release sites. J Chem Neuroanat. 1997; 13(4):219-41. DOI: 10.1016/s0891-0618(97)00051-3. View

Azkue J, Mateos J, Elezgarai I, Benitez R, Osorio A, Diez J . The metabotropic glutamate receptor subtype mGluR 2/3 is located at extrasynaptic loci in rat spinal dorsal horn synapses. Neurosci Lett. 2000; 287(3):236-8. DOI: 10.1016/s0304-3940(00)01189-7. View

Dietrich D, Kral T, Clusmann H, Friedl M, Schramm J . Presynaptic group II metabotropic glutamate receptors reduce stimulated and spontaneous transmitter release in human dentate gyrus. Neuropharmacology. 2002; 42(3):297-305. DOI: 10.1016/s0028-3908(01)00193-9. View

Erb S, Stewart J . A role for the bed nucleus of the stria terminalis, but not the amygdala, in the effects of corticotropin-releasing factor on stress-induced reinstatement of cocaine seeking. J Neurosci. 1999; 19(20):RC35. PMC: 6782764. View

Bossert J, Liu S, Lu L, Shaham Y . A role of ventral tegmental area glutamate in contextual cue-induced relapse to heroin seeking. J Neurosci. 2004; 24(47):10726-30. PMC: 6730135. DOI: 10.1523/JNEUROSCI.3207-04.2004. View

Baker D, McFarland K, Lake R, Shen H, Tang X, Toda S . Neuroadaptations in cystine-glutamate exchange underlie cocaine relapse. Nat Neurosci. 2003; 6(7):743-9. DOI: 10.1038/nn1069. View

Moldrich R, Jeffrey M, Talebi A, Beart P, Chapman A, Meldrum B . Anti-epileptic activity of group II metabotropic glutamate receptor agonists (--)-2-oxa-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY379268) and (--)-2-thia-4-aminobicyclo[3.1.0]hexane-4,6-dicarboxylate (LY389795). Neuropharmacology. 2001; 41(1):8-18. DOI: 10.1016/s0028-3908(01)00044-2. View

Kim J, Austin J, Tanabe L, Creekmore E, Vezina P . Activation of group II mGlu receptors blocks the enhanced drug taking induced by previous exposure to amphetamine. Eur J Neurosci. 2005; 21(1):295-300. DOI: 10.1111/j.1460-9568.2004.03822.x. View

Aultman J, Moghaddam B . Distinct contributions of glutamate and dopamine receptors to temporal aspects of rodent working memory using a clinically relevant task. Psychopharmacology (Berl). 2001; 153(3):353-64. DOI: 10.1007/s002130000590. View

10.

Cartmell J, Monn J, Schoepp D . Attenuation of specific PCP-evoked behaviors by the potent mGlu2/3 receptor agonist, LY379268 and comparison with the atypical antipsychotic, clozapine. Psychopharmacology (Berl). 2000; 148(4):423-9. DOI: 10.1007/s002130050072. View

11.

Tyler E, Lovinger D . Metabotropic glutamate receptor modulation of synaptic transmission in corticostriatal co-cultures: role of calcium influx. Neuropharmacology. 1995; 34(8):939-52. DOI: 10.1016/0028-3908(95)00066-f. View

12.

Baptista M, Martin-Fardon R, Weiss F . 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. J Neurosci. 2004; 24(20):4723-7. PMC: 6729475. DOI: 10.1523/JNEUROSCI.0176-04.2004. View

13.

Moran M, McFarland K, Melendez R, Kalivas P, Seamans J . Cystine/glutamate exchange regulates metabotropic glutamate receptor presynaptic inhibition of excitatory transmission and vulnerability to cocaine seeking. J Neurosci. 2005; 25(27):6389-93. PMC: 1413952. DOI: 10.1523/JNEUROSCI.1007-05.2005. View

14.

Lombardi G, Pellegrini-Giampietro D, Leonard P, CHERICI G, Pellicciari R, Moroni F . The depolarization-induced outflow of D-[3H]aspartate from rat brain slices is modulated by metabotropic glutamate receptors. Neurochem Int. 1994; 24(6):525-32. DOI: 10.1016/0197-0186(94)90003-5. View

15.

Petralia R, Wang Y, Niedzielski A, Wenthold R . The metabotropic glutamate receptors, mGluR2 and mGluR3, show unique postsynaptic, presynaptic and glial localizations. Neuroscience. 1996; 71(4):949-76. DOI: 10.1016/0306-4522(95)00533-1. View

16.

Grueter B, Winder D . Group II and III metabotropic glutamate receptors suppress excitatory synaptic transmission in the dorsolateral bed nucleus of the stria terminalis. Neuropsychopharmacology. 2005; 30(7):1302-11. DOI: 10.1038/sj.npp.1300672. View

17.

Testa C, Friberg I, Weiss S, Standaert D . Immunohistochemical localization of metabotropic glutamate receptors mGluR1a and mGluR2/3 in the rat basal ganglia. J Comp Neurol. 1998; 390(1):5-19. View

18.

Shalev U, Morales M, Hope B, Yap J, Shaham Y . Time-dependent changes in extinction behavior and stress-induced reinstatement of drug seeking following withdrawal from heroin in rats. Psychopharmacology (Berl). 2001; 156(1):98-107. DOI: 10.1007/s002130100748. View

19.

Schoepp D . Novel functions for subtypes of metabotropic glutamate receptors. Neurochem Int. 1994; 24(5):439-49. DOI: 10.1016/0197-0186(94)90092-2. View

20.

Defagot M, Villar M, Antonelli M . Differential localization of metabotropic glutamate receptors during postnatal development. Dev Neurosci. 2002; 24(4):272-82. DOI: 10.1159/000066741. View