EXPRESSION AND PRESENCE OF SEPTAL NEUROKININ-2 RECEPTORS CONTROLLING HIPPOCAMPAL ACETYLCHOLINE-RELEASE DURING SENSORY STIMULATION IN RAT

We examined the expression and presence of NK2 receptors in the septal area of rat brain, and investigated their functional role in the regu lation of the septohippocampal cholinergic system. Using reverse trans cription-polymerase chain reaction (RT-PCR) analysis, we showed the pr esence of NK2 receptor mRNA expression in the septal area, and detecte d septal NK2 binding sites by using a fluorescent-tagged neurokinin A (NKA) derivative. In vivo microdialysis was employed to explore the fu nctional role of NK2 receptors in the release of hippocampal acetylcho line evoked by tactile stimulation in freely moving rats. Two sessions of stroking of the neck and back of the rat for 30 min, at 90 min int ervals, produced a marked and reproducible increase in hippocampal ace tylcholine release. This effect was dose-dependently prevented by intr aperitoneal administration of the two selective non-peptide tachykinin NK2 receptor antagonists SR144190 (0.03-0.3 mg/kg, i.p.) and SR48968 (0.3 and 1 mg/kg, i.p.), but not by the inactive enantiomer of SR48968 (SR48965, 1 mg/kg) nor by the two non-peptide NK1 receptor antagonist s SR140333 (3 mg/kg, i.p.) and GR205171 (1 mg/kg, i.p.). Furthermore, the intraseptal application of SR144190 (10(-8) M) reduced the sensory response. Finally, intraseptal perfusion of neurokinin A (0.01-10 mu M) in anaesthetized rats produced a concentration-dependent increase i n hippocampal acetylcholine release. The response to neurokinin A (0.1 mu M) was prevented by SR144190 (0.03-0.3 mg/kg, i.p.) and SR48968 (0 .3-1 mg/kg, i.p.). In conclusion, this study provides direct evidence for the role of endogenous NKA/substance P, through the activation of NK2 receptors, in regulating the septohippocampal cholinergic function .