Neurotensin counteracts apomorphine-induced inhibition of dopamine release as studied by microdialysis in rat neostriatum.
Microdialysis in the neostriatum of the halothane-anesthetized male rats was used to study the effect of neurotensin on the release of dopamine and its metabolites in the absence or presence of systemic apomorphine treatment. Perfusate levels of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were assayed by high-performance liquid chromatography in combination with electrochemical detection. Perfusion with neurotensin (1000 nM but not 10 nM) increased the dialysate levels of dopamine without affecting those of DOPAC and HVA. Systemic treatment with apomorphine (0.05 and 0.5 mg/kg, s.c.) reduced the dialysate levels of dopamine, DOPAC and HVA in a dose-related way. Neurotensin (10 nM but not 1 nM) counteracted the inhibitory effect of apomorphine on dialysate levels of dopamine without affecting those of DOPAC and HVA. The results indicate a facilitatory effect of neurotensin on dopamine release in rat neostriatum. It is suggested that activation of neurotensin receptors may cause a reduction in the affinity of dopamine autoreceptors, since the low dose of neurotensin is able to counteract the inhibitory effect of apomorphine on dopamine release.
Tanganelli
S
S
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
von Euler
G
G
Fuxe
K
K
Agnati
L F
LF
Ungerstedt
U
U
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013779:Tetrodotoxin / Q000494:pharmacology
D015102:3,4-Dihydroxyphenylacetic Acid; D009496:Neurotensin; D013779:Tetrodotoxin; D010042:Ouabain; D001058:Apomorphine; D004298:Dopamine; D006719:Homovanillic Acid