DIFFERENTIAL-EFFECTS OF INTRASTRIATAL NEUROTENSIN(1-13) AND NEUROTENSIN(8-13) ON STRIATAL DOPAMINE AND PALLIDAL GABA RELEASE - A DUAL-PROBEMICRODIALYSIS STUDY IN THE AWAKE RAT

In the present dual-probe microdialysis study the effects of intrastri atal perfusion with the tridecapeptide neurotensin(1-13) [NT(1-13)] an d its active fragment NT(8-13) on striatopallidal GABA and striatal do pamine release were investigated. The modulatory action of NT(1-13) on D-2 receptor-mediated inhibition of striatal and pallidal GABA releas e 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 intrast riatal perfusion with the neurotensin receptor antagonist SR48692 (100 nM). A similar increase (155%) in striatal dopamine release was obser ved following intrastriatal NT(1-13) (100 nM), but not NT(8-13) (100 a nd 500 nM). However, at the highest concentration studied (1 mu M) NT( 8-13) was associated with a rapid increase (130%) in striatal dopamine release. In a second study intrastriatal NT(1-13) (10 nM) counteracte d the inhibition of striatal and pallidal GABA release induced by perg olide (500 and 1500 nM). The inhibitory action of the D-2 agonist was restored when SR48692 (100 nm) was added to the perfusion medium. Thes e results suggest that in the neostriatum the neurotensin receptor loc ated postsynaptically on the striatopallidal GABA neurons seems to dif fer from the neurotensin receptor located on dopaminergic terminals, a s indicated by the relative lack of effect of NT(8-13) on striatal dop amine release. furthermore, the ability of NT(1-13) to counteract the pergolide-induced inhibition of both striatal and pallidal GABA releas e strengthens the evidence for antagonistic receptor-receptor interact ion between postsynaptic striatal neurotensin and De receptors located on striatopallidal GABA neurons.