Effects of ketamine and n-methyl-d-aspartate on glutamate and dopamine release in the rat prefrontal cortex: modulation by a group II selective metabotropic glutamate receptor agonist LY379268

Clozapine and Haloperidol Differently Suppress the MK-801-Increased Glutamatergic and Serotonergic Transmission in the Medial Prefrontal Cortex of the Rat

“…Consistent with our findings, it has been shown that blockade of AMPA/kainate receptors in the prefrontal cortex inhibited PCP-induced locomotion and stereotypy (Takahata and Moghaddam, 2003). Thus, in line with previous reports (Moghaddam et al, 1997;Adams and Moghadam, 2001;Lorrain et al, 2003), MK-801 increases glutamate release onto AMPA/kainate receptors, which, in turn, elicit an enhanced glutamatergic output from mPFC neurons, including those projecting to the dorsal raphe nucleus, thereby increasing serotonergic cell firing and cortical 5-HT efflux. Although this functional interplay between the mPFC and the dorsal raphe nucleus is well documented (Hajós et al, 1998;Celada et al, 2001;Martín-Ruiz et al, 2001;Amargós-Bosch et al, 2003;Lucas et al, 2005), we presently cannot rule out the possibility of a direct effect of MK-801 on serotonergic neurons of the dorsal raphe nucleus (Callado et al, 2000;Tao and Auerbach, 2000) and its blockade downstream by NBQX acting on AMPA receptors putatively located in serotonergic terminals Effect of clozapine and haloperidol X Ló pez-Gil et al (Maione et al, 1997).…”

“…Nevertheless, the present study evidenced that MK-801-stimulated glutamate efflux is largely TTX dependent, that is released from neurons in an impulse-dependent manner. This is in line with previous work showing that the efflux of glutamate elicited by ketamine was also fully dependent on nerve impulse (Lorrain et al, 2003). It remains to be determined, however, the provenance of NMDA receptor antagonist-stimulated extracellular glutamate in the mPFC.…”

“…It remains to be determined, however, the provenance of NMDA receptor antagonist-stimulated extracellular glutamate in the mPFC. The fact that local perfusion of PCP, ketamine, and MK-801 in the mPFC failed to elicit the increase in glutamate and/or 5-HT (Lorrain et al, 2003;Amargós-Bosch et al, 2006, this study) indicates that the NMDA receptors responsible for these effects are located outside the mPFC. Our results are consistent with other data showing that the increased locomotion and firing or EPSCs of putative pyramidal neurons of the mPFC following systemic administration of NMDA receptor antagonists (Suzuki et al, 2002;Jodo et al, 2003;Jackson et al, 2004) were not mimicked by intra-mPFC application of these compounds (Aghajanian and Marek, 2000;Suzuki et al, 2002;Jodo et al, 2005).…”

“…Furthermore, the behavioral deficits observed in humans and rodents are distinctly responsive to clozapine (Bakshi et al, 1994;Maurel-Remy et al, 1995;Malhotra et al, 1997). Acute NMDA receptor antagonism has also been reported to increase the release of glutamate (Moghaddam et al, 1997;Adams and Moghadam, 2001;Lorrain et al, 2003), dopamine (Moghaddam and Adams, 1998;Mathé et al, 1999;Schmidt and Fadayel, 1996), and serotonin (5-HT) (Martin et al, 1998;Millan et al, 1999;Adams and Moghadam, 2001;Amargós-Bosch et al, 2006) in the medial prefrontal cortex (mPFC) of rats. These effects are coincident with an enhanced spontaneous firing rate of putative pyramidal neurons of the mPFC (Suzuki et al, 2002;Jackson et al, 2004).…”

Chronic Phenethylamine Hallucinogen Treatment Alters Behavioral Sensitivity to a Metabotropic Glutamate 2/3 Receptor Agonist

“…Group II mGlu receptors, mGlu2 and mGlu3 subtypes, couple through G i/o to various effector pathways, including inhibition of adenylyl cyclase and regulation of ion channels. Through such mechanisms, presynaptic mGlu2/3 receptors may reduce glutamatergic neurotransmission in brain regions where excessive glutamatergic neurotransmission has been implicated in the pathophysiology of schizophrenia (Moghaddam and Adams, 1998;Lorrain et al, 2003). Additionally, the behavioral effects of the psychotomimetic drug ketamine in humans are disrupted by an mGlu2/3 receptor agonist (Krystal et al, 2005) and a recent phase II clinical trial shows that an mGlu2/3 receptor agonist is an effective antipsychotic therapy, comparable to the atypical antipsychotic drug, olanzapine (Patil et al, 2007).…”