EFFECT OF NEUROTENSIN AND IMMUNONEUTRALIZATION WITH ANTI-NEUROTENSIN-SERUM ON DOPAMINERGIC CHOLINERGIC INTERACTION IN THE STRIATUM

The effect of neurotensin (NT) on the release of acetylcholine (ACh) a nd dopamine (DA) from striatal slices of the rat brain was studied. Ne urotensin, 1-150 nM, was able to release ACh from cholinergic interneu rons of the striatum. Like the response to electrical stimulation, the ACh-releasing effect of NT was completely inhibited by tetrodotoxin i ndicating that neuronal firing is involved in its effect. Immunneutril ization reduced the stimulation-evoked release of ACh, an effect that was much marked when the inhibitory dopaminergic input was suspended b y sulpiride-selective antagonists of D2 receptors. Sulpiride, 0.1 mM, induced a 2-fold increase in the NT- and electrically-induced release of ACh. A quantitatively similar increase was also observed after dege neration of the nigrostriatal DA pathway with 6-hydroxydopamine (6-OHD A) (2 x 250 mug/animal, i.c.v.). However, the D2 receptor agonist quin pirole, 0.01 mM, significantly reduced the NT-induced release of ACh b y 77%. Neurotensin enhanced the stimulation-evoked release of [H-3]DA. These findings indicate that, using field stimulation when dopaminerg ic, cholinergic and NT-containing neurons are stimulated in concert, N T is capable of releasing both ACh and DA in the striatum, but its eff ect on ACh release is masked unless the D2 receptor-mediated tonic inh ibitory effect of DA released from the nigro-striatal pathway is atten uated. Thus, in Parkinson's disease where the dopaminergic input is im paired, NT may be involved in producing cholinergic dominance.