Facilitatory role of somatostatin via muscarinic cholinergic system in the generation of long-term potentiation in the rat dentate gyrus in vivo.
We investigated whether somatostain modulates the generation of long-term potentiation (LTP) in rat perforant path-dentate gyrus synapse in vivo. When somatostatin was injected intracerebroventricularly (i.c.v.) 20 min prior to the tetanus, the intensity of LTP increased dose dependently. Synaptic potential evoked by a low-frequency test stimulation, however, was not altered by somatostatin. We next tested whether the LTP-augmenting effect of somatostain is mediated by cholinergic activation, because somatostatin was demonstrated to promote acetylcholine release in rat hippocampal slice. Pirenzepine (50 nmol/rat), a muscarinic M1 receptor antagonist, did not affect the tetanus-induced LTP by itself. But when it was co-applicated with the somatostatin (50 ng/rat) 20 min before tetanus, it completely abolished the LTP-augmenting effect of somatostatin. Then we examined the effect of octreotide, a potent agonist specifically binding to somatostatin receptor subtypes 2 and 4, on the generation of LTP. Octreotide (500 ng/rat) also facilitated the intensity of LTP. These results suggest that somatostatin facilitates the generation of perforant path-dentate gyrus granule cell LTP by activating the muscarinic cholinergic receptor and the effect of somatostatin is induced, at least partly, by somatostatin receptor subtypes 2 and 4 in vivo.
Nakata
A
A
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Saito
H
H
Nishiyama
N
N
D000818:Animals; D018891:Dentate Gyrus / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D010890:Pirenzepine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology*
D011976:Receptors, Muscarinic; D010890:Pirenzepine; D013004:Somatostatin