Long-term treatment with l-DOPA and an mGlu5 receptor antagonist prevents changes in brain basal ganglia dopamine receptors, their associated signaling proteins and neuropeptides in parkinsonian monkeys.
We injected rats three times at 3 h intervals (from 0900 h to 1500 h) with the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 at 0.1 or 0.5 mg/kg of body weight. Three hours after the last injection, animals were sacrificed and the brains were processed for in situ hybridization histochemistry. Preproenkephalin (PPE) mRNA levels were significantly decreased throughout the caudate-putamen (CPu) and nucleus accumbens (NAc) at the lower dose. The higher dose produced significant decreases only in anterior CPu (aCPu) and NAc. Concurrent administration of the muscarinic cholinergic receptor antagonist scopolamine at 2 or 5 mg/kg neither potentiated nor prevented the effect of MK-801 on PPE mRNA levels in the neostriatum. In contrast, co-administration of haloperidol (dopamine receptor antagonist) with MK-801 blocked the effect of the latter in the NAc, and elevated PPE mRNA levels throughout the CPu. The data demonstrate that the acute effects of glutamate receptor activity on striatal and accumbal PPE mRNA expression via the NMDA receptor can be modulated by the dopaminergic system in the brain of the rat.