PHARMACOLOGICAL CHARACTERIZATION OF TACHYKININ RECEPTORS CONTROLLING ACETYLCHOLINE-RELEASE FROM RAT STRIATUM - AN IN-VIVO MICRODIALYSIS STUDY

The regulation of striatal cholinergic function by tachykinins was exa mined in urethane-anesthetized rats by using microdialysis. Substance P (0.01-1 mu M), [Sar(9),Met(O-2)(11)] substance P (1-10 mu M), septid e (0.1-3 mu M), neurokinin (NK) A (0.1-10 mu M), and senktide (0.1-10 mu M) produced concentration-dependent increases in striatal acetylcho line (ACh) release. Septide was the most potent agonist for inducing r elease of ACh, whereas the stimulating effect of senktide was less pro nounced and more progressive in onset. The response to septide was pre vented by intraperitoneal administration of the nonpeptide NK1 antagon ist SR 140333 (1-3 mg/kg) but not by the nonpeptide NK2 receptor antag onist SR 48968, indicating that the effect was mediated specifically b y NK1 receptors. ACh release caused by NKA was reduced by SR 48968 (1- 3 mg/kg) and slightly affected by SR 140333, indicating a principal ro le for NK2 receptors in the peptide response. The similar efficacy of SR 140333 and SR 48968 in blocking substance P-induced ACh release sug gested that the effect of this peptide involves the stimulation of bot h NK1 and NK2 receptors. Finally, our results indicate that the increa se in striatal ACh release induced by the D-1 agonist (+)-SKF-38393 (3 mu M) may be mediated indirectly through local release of NKA or subs tance P acting at NK2 receptors.