Metabotropic Glutamate Receptors in the Rat Nucleus Accumbens

Abstract

The effects of glutamate metabotropic receptors (mGluRs) on excitatory transmission in the nucleus accumbens were investigated using electrophysiological techniques in rat nucleus accumbens slices. The broad-spectrum mGluR agonist (1S,3R)-1-aminocyclopentyl-1,3-dicarboxylate, the mGluR group 2 selective agonists (S)-4-carboxy-3-hydroxyphenylglycine, (1S,3S)-ACPD) and (2S,1'S,2'S)-2-(2'-carboxycyclopropyl)glycine (L-CCG1), and the mGluR group 3 specific agonist L-2-amino-4-phosphonobutyrate (L-AP4) all reversibly inhibited evoked excitatory synaptic responses. The specific group 1 mGluR agonist (R,S)-3,5-dihydroxyphenylglycine [(R,S)-DHPG] did not depress transmission. Dose-response curves showed that the rank order of agonist potencies was: L-CCG1 > L-AP4 > (1S,3S)-ACPD. Group 2 and 3 mGluRs inhibited transmission via a presynaptic mechanism, as they increased paired-pulse facilitation, decreased the frequency of miniature excitatory postsynaptic currents and had no effect on their amplitude. The mGluRs did not inhibit transmitter release by reducing voltage-dependent Ca2+ currents through N- or P-type Ca2+ channels, as inhibition persisted in the presence of omega-conotoxin-GVIA or omega-Aga-IVA. The depression induced by mGluRs was not affected by specific antagonists of dopamine D1, GABA-B or adenosine A1 receptors, indicating direct effects. Finally, (R,S)-DHPG specifically blocked the postsynaptic afterhyperpolarization current (I(AHP)). Our results represent the first direct demonstration of functional mGluRs in the nucleus accumbens of the rat.

The Metabotropic Glutamate 2/3 Receptor Agonist LY379268 Blocked Nicotine-Induced Increases in Nucleus Accumbens Shell Dopamine only in the Presence of a Nicotine-Associated Context in Rats

“…Because mGlu2/3 receptor activation negatively regulates glutamatergic neurotransmission (Cartmell and Schoepp, 2000), we hypothesized that LY379268 decreases the reinforcing effects of nicotine by attenuating nicotineinduced increases in NAcc shell dopamine. This hypothesis is supported by the observation that mGlu2/3 receptors are expressed in the NAcc shell (Testa et al, 1998), and these receptors regulate both basal and psychostimulantinduced NAcc dopamine neurotransmission (Greenslade and Mitchell, 2004;Hu et al, 1999;Karasawa et al, 2006;Kim et al, 2005;Manzoni et al, 1997;Uslaner et al, 2009;Xi et al, 2002aXi et al, , 2010a. Furthermore, activation of mGlu2/3 receptors attenuated the dopamine-dependent psychostimulant-induced enhancement of locomotor activity (Kim et al, 2005;Riegel et al, 2003).…”

Activation of Group II Metabotropic Glutamate Receptors in the Nucleus Accumbens Shell Attenuates Context-Induced Relapse to Heroin Seeking

“…Results from anatomical studies do not indicate differential distribution of mGluR 2 or mGluR 3 receptors in the NAc core, shell, and striatum (Petralia et al, 1996;Ohishi et al, 1998;Richards et al, 2005). In the NAc, agonist activation of mGluR 2/3 receptors decreases excitatory synaptic transmission via presynaptic mechanisms (Manzoni et al, 1997) and decreases glutamate levels, as measured by microdialysis . Based on the above findings, a plausible interpretation of the present data is that exposure to the heroin context increases excitatory glutamate transmission in the NAc shell and this effect is reversed by local injections of LY379268.…”

Toluene-Induced Locomotor Activity is Blocked by 6-Hydroxydopamine Lesions of the Nucleus Accumbens and the mGluR2/3 Agonist LY379268

“…Moreover, the application of the nonselective mGluR agonist t-ACPD directly into the NAC blocked PFC-or VTA-electrical stimulation-induced increases in NAC DA (Taber and Fibiger, 1995). Also, the superfusion of selective mGluR3 agonists such as L-AP4 onto accumbal slices is reported to inhibit DA release (Manzoni et al, 1997). While an LY379268-PFC mechanism cannot be ruled out, it appears unlikely.…”