Tyrosine hydroxylase increases in locus coeruleus after chronic NMDA blockade in the ventral striatum
Lelutiu, Nadia B
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Olfactory bulbectomy (OBX) results in many neurochemical and behavioral changes that model depression. To test the possibility that glutamatergic dysfunction causes these changes, the present study aimed to create a pharmacological manipulation that would be comparable to the OBX model. To this end, we chronically injected the competitive NMDA antagonist, AP-5 (2.5, 5.0, or 10.0µg/day) directly into the olfactory tubercle for a period of 14-17 days followed by in situ hybridization measuring galanin (GAL) and tyrosine hydroxylase (TH) mRNA in the locus coeruleus (LC). Autoradiography revealed that TH mRNA levels were significantly increased in the LC of rats in the AP-5 10.0µg/day group compared to all other groups. No significant change was found in GAL mRNA levels. These results suggest that glutamatergic disruption in the ventral striatum leads to increased NE activity in the LC, thereby stimulating dopaminergic activity in the VTA, which may result in the hyperactive locomotor response observed following this manipulation or OBX.