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d-amphetamine-induced increase in neurotensin and neuropeptide Y outflow in the ventral striatum is mediated via stimulation of dopamine D1 and D2/3 receptors

✍ Scribed by Susanne H.M. Gruber; George G. Nomikos; Aleksander A. Mathé


Publisher
John Wiley and Sons
Year
2002
Tongue
English
Weight
103 KB
Volume
69
Category
Article
ISSN
0360-4012

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✦ Synopsis


The neuroanatomical and functional relationships between dopamine (DA) and neurotensin (NT) and DA and neuropeptide Y (NPY) suggest a role for these neuropeptides in DA-related neuropsychiatric disorders. By employing a microdialysis technique in conjunction with radioimmunoassay (RIA), the effects of d-amphetamine per se or after pretreatment with DA receptor antagonists on NT and NPY outflow were determined in the ventral striatum (VSTR) of the rat. One hour after a subcutaneous (s.c.) injection of saline, the DA-D(1) receptor antagonist SCH 23390 (0.3 mg/kg), or the DA-D(2/3) receptor antagonist raclopride (1.0 mg/kg), animals were injected s.c. with either saline or d-amphetamine (1.5 mg/kg). d-Amphetamine significantly increased extracellular NT- and NPY-like immunoreactivity (LI) concentrations compared with control animals. Administration of SCH 23390 or raclopride did not significantly affect NT-LI or NPY-LI concentrations. However, pretreatment with either SCH 23390 or raclopride abolished the stimulatory effect of d-amphetamine on NT-LI and NPY-LI. These findings demonstrate that d-amphetamine increases extracellular concentrations of NT-LI and NPY-LI in the VSTR through a mechanism that initially involves stimulation of either DA-D(1) or DA-D(2/3) receptors but appears to require both. In conclusion, changes in dopaminergic neurotransmission via DA-D(1) and DA-D(2/3) receptors affect the outflow of both NT and NPY in the VSTR.