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

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‐D1 receptor antagonist SCH 23390 (0.3 mg/kg), or the DA‐D2/3 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‐D1 or DA‐D2/3 receptors but appears to require both. In conclusion, changes in dopaminergic neurotransmission via DA‐D1 and DA‐D2/3 receptors affect the outflow of both NT and NPY in the VSTR. © 2002 Wiley‐Liss, Inc.