Differential effects of intrastriatal neurotensin(1-13) and neurotensin(8-13) on striatal dopamine and pallidal GABA release. A dual-probe microdialysis study in the awake rat.
In the present dual-probe microdialysis study the effects of intrastriatal perfusion with the tridecapeptide neurotensin(1-13) [NT(1-13)] and its active fragment NT(8-13) on striatopallidal GABA and striatal dopamine release were investigated. The modulatory action of NT(1-13) on D2 receptor-mediated inhibition of striatal and pallidal GABA release was also studied. Both intrastriatal NT(1-13) (100 nM) and NT(8-13) (100 nM) increased striatal (139 and 149% respectively) and pallidal (130 and 164%) GABA release, and this effect was antagonized by intrastriatal perfusion with the neurotensin receptor antagonist SR48692 (100 nM). A similar increase (155%) in striatal dopamine release was observed following intrastriatal NT(1-13) (100 nM), but not NT(8-13) (100 and 500 nM). However, at the highest concentration studied (1 microM) NT(8-13) was associated with a rapid increase (130%) in striatal dopamine release. In a second study intrastriatal NT(1-13) (10 nM) counteracted the inhibition of striatal and pallidal GABA release induced by pergolide (500 and 1500 nM). The inhibitory action of the D2 agonist was restored when SR48692 (100 nM) was added to the perfusion medium. These results suggest that in the neostriatum the neurotensin receptor located postsynaptically on the striatopallidal GABA neurons seems to differ from the neurotensin receptor located on dopaminergic terminals, as indicated by the relative lack of effect of NT(8-13) on striatal dopamine release. Furthermore, the ability of NT(1-13) to counteract the pergolide-induced inhibition of both striatal and pallidal GABA release strengthens the evidence for antagonistic receptor-receptor interaction between postsynaptic striatal neurotensin and D2 receptors located on striatopallidal GABA neurons.
Ferraro
L
L
Department of Experimental and Clinical Medicine, University of Ferrara, Italy.
O'Connor
W T
WT
Antonelli
T
T
Fuxe
K
K
Tanganelli
S
S
D000818:Animals; D003342:Corpus Striatum / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005917:Globus Pallidus / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D017551:Microdialysis / Q000379:methods; D009496:Neurotensin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010477:Perfusion; D010479:Pergolide / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D010446:Peptide Fragments; D011720:Pyrazoles; D011804:Quinolines; D018028:Receptors, Neurotensin; C079087:SR 48692; D010479:Pergolide; D009496:Neurotensin; D005680:gamma-Aminobutyric Acid; C054381:neurotensin (8-13); D004298:Dopamine