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-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.
Institution of Clinical Neuroscience, St. Görans Hospital, Karolinska Institutet, Stockholm, Sweden.
Susanne H M
SH
Gruber
George G
GG
Nomikos
Aleksander A
AA
Mathé
D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects* / Q000378:metabolism; D003913:Dextroamphetamine / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D009478:Neuropeptide Y / Q000096:biosynthesis*; D009496:Neurotensin / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000096:biosynthesis*; D017448:Receptors, Dopamine D2 / Q000096:biosynthesis*; D050637:Receptors, Dopamine D3
D018765:Dopamine Uptake Inhibitors; C493595:Drd3 protein, rat; D009478:Neuropeptide Y; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D050637:Receptors, Dopamine D3; D009496:Neurotensin; D003913:Dextroamphetamine