Dopamine receptor antagonists prevent the d-amphetamine-induced increase in calcitonin gene-related peptide levels in ventral striatum.
Microdialysis in conjunction with radioimmunoassay (RIA) were used to study the effects of acute d-amphetamine or dopamine (DA) receptor antagonists administration on extracellular concentrations of calcitonin gene-related peptide (CGRP) in the ventral striatum of the rat. One hour after the 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), one additional s.c. injection of saline or d-amphetamine (1.5 mg/kg) was given. The dialysates were collected at 60-min intervals; CGRP-like immunoreactivities (-LI) were determined by RIA. d-Amphetamine significantly increased extracellular CGRP-LI concentrations compared to the control animals. Administration of either SCH 23390 or raclopride did not significantly affect CGRP-LI concentrations. Pretreatment with either SCH 23390 or raclopride abolished the stimulatory effect of d-amphetamine on CGRP-LI levels. The results show that d-amphetamine administration results in an increase in extracellular concentrations of CGRP in the ventral striatum through a mechanism that appears to involve stimulation of either DA-D(1) or DA-D(2/3) receptors. The results also indicate that changes in dopaminergic neurotransmission affect CGRP outflow in the ventral striatum in a phasic but not tonic manner.
Gruber
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SH
Institution of Clinical Neuroscience, Karolinska Institutet, St. Görans Hospital, Stockholm, Sweden.
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D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000378:metabolism*; D001552:Benzazepines / Q000494:pharmacology*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D003913:Dextroamphetamine / Q000494:pharmacology; D018492:Dopamine Antagonists / Q000494:pharmacology*; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D008297:Male; D017551:Microdialysis; D020891:Raclopride / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D001552:Benzazepines; D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D020891:Raclopride; D015740:Calcitonin Gene-Related Peptide; D003913:Dextroamphetamine