SDZ-ENS-163, A SELECTIVE MUSCARINIC M1 RECEPTOR AGONIST, FACILITATES THE INDUCTION OF LONG-TERM POTENTIATION IN RAT HIPPOCAMPAL SLICES

The effect of SDZ ENS 163; (+)-(3S,cis)-3-ethyldihydro-4-[(1-methyl-1H-imidazol-5-yl)methyl-2(3H)-thiphenonedihydrogenphosphate), a selective muscarinic M1 agonist, on long-term potentiation (LTP) was studied in a rat hippocampal slice preparation. LTP was induced by theta-burst stimulation (TBS) delivered to the Schaffer/commissural fibers. In untreated slices delivery of 8 or 10 trains at 100 Hz induced a 27 +/- 8.3 and 54 +/- 7.2% potentiation of the amplitude of the excitatory postsynaptic potential (epsp), respectively (calculated as percentage of the pre-LTP amplitude). In slices pretreated with SDZ ENS 163 (2 X 10(-6) M, - 30 min) delivery of 8 or 10 trains at 100 Hz induced a 62 +/- 8.4 and 54 +/- 7.1% potentiation of the epsp amplitude, respectively. In addition, treatment with SDZ ENS 163 (2 X 10(-6) M) increased the N-methyl-D-aspartate receptor-induced component of the epsp response to TBS from 21 +/- 3 (control) to 33 +/- 2%. Pretreatment with the muscarinic antagonist, scopolamine (6 X 10(-8) M), or with the M1 selective muscarinic receptor antagonist, pirenzepine (6 X 10(-8) M), did not affect LTP in untreated slices but inhibited the enhancement of LTP by SDZ ENS 163 (2 X 10(-6) M) completely. AF-DX 116 (10(-6) M, - 60 min), a selective muscarinic M2 receptor antagonist did not affect LTP in control slices nor in slices treated with SDZ ENS 163 (2 X 10(-6) M). These data suggest that activation of muscarinic M1 receptors by SDZ ENS 163 facilitates the induction of LTP.