Impoverished Rearing Environment Alters Metabotropic Glutamate Receptor Expression and Function in the Prefrontal Cortex

Abstract

Rearing rats in impoverished (IC) and enriched (EC) environmental conditions alters synaptic plasticity and cognitive processes. Metabotropic glutamate receptors (mGluRs) are known to play a key role in synaptic and behavioral plasticity. In the present study, the effect of rearing conditions on the expression of mGluR proteins in the prefrontal cortex (PFC) was assessed by immunoblotting. A significant difference in the content of prefrontal mGluR1 and mGluR5 (ie group I) and mGluR2/3 (ie group II) was observed between IC and EC rats. To functionally characterize this difference, in vivo microdialysis was used to verify differences in mGluR regulation of extracellular glutamate in the PFC. The results indicate that the capacity of group I and II mGluRs to elevate extracellular glutamate levels was significantly blunted in the PFC of IC rats compared to either EC subjects, or rats reared in normal environmental conditions (ie NIH standards). Group II mGluR receptors regulate performance in a forced T-maze spatial memory task that involves the PFC, and IC rats demonstrated deficits in this task relative to EC rats. These data suggest that reduced mGluR transmission in the PFC produced by impoverished, relative to enriched, rearing environments may contribute to cognitive deficits.

Environmental enrichment increases amphetamine-induced glutamate neurotransmission in the nucleus accumbens: A neurochemical study

“…Values were not corrected for in vitro probe recovery efficiency, which was ~15% and in close agreement with published values (Melendez et al, 2004). The baseline was defined as the average glutamate or aspartate level in three samples prior to the saline injection and normalized to 100%.…”

“…Samples were analyzed for glutamate and aspartate levels using high performance liquid chromatography coupled with electrochemical detection (HPLC-ECD, ESA Inc., Chelmsford, MA) as previously described (Melendez et al, 2004). The system consisted of a solvent delivery unit, a Coulochem III electrochemical detector equipped with a 5014B analytical cell and 5020 guard cell.…”

“…Enrichment has been shown to increase neurogenesis (Nilsson et al, 1999;Segovia et al, 2006), increase dendritic spines on medium size spiny neurons (Comery et al, 1996), increase synaptic density (Rampon et al, 2000) and increase the density of astrocytes (Pham et al, 1999). It is possible that these enrichment-induced modifications are associated with synaptic plasticity within the brain reward circuitry where glutamate neurotransmission plays a modulatory role (Wolf, 1998;Wolf and Xue, 1999;Giorgetti et al, 2001;Melendez et al, 2004).…”

“…Environmental enrichment has been found to alter DA function in NAcc in response to psychostimulants (Bardo et al, 1999;Zhu et al, 2004), as well as to alter glutamate function in hippocampus and medial prefrontal cortex (Melendez et al, 2004;Naka et al, 2005). Compared to IC rats, EC rats have reduced subunit expression for N-methyl-D-aspartate (NMDA) receptors, but not α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptors (Wood et al, 2005), perhaps reflecting a subtype-specific down-regulation in response to an enhanced glutamate signal.…”

Advances in the treatment of anxiety: Targeting glutamate

“…This same compound was as effective as alprazolam in preventing lactate-induced anxiety in panic-prone rats, 154 in blocking fear-potentiated startle in rats 155 and humans, 138 and CO 2 -provoked anxiety in human patients with panic disorder. 156 A recent report shows changes in group I and group II metabotropic receptor expression in the prefrontal cortex of rats exposed to an impoverished rearing environment, 157 and just as imipramine causes downregulation of mGluR1 receptors, it also mediated upregulation of hippocampal mGluR2/3. 158 Finally, group II metabotropic agonists have been shown, like lamotrigine (see above), to decrease the motor and cognitive effects of NMDA antagonists such as phencyclidine (which increases glutamate neurotransmission via non-NMDA receptors.)…”