Interactive effects of AM251 and baclofen on synaptic plasticity in the rat dentate gyrus.
Long-term potentiation (LTP), a form of synaptic plasticity, is considered to be a critical cellular mechanism that underlies learning and memory. Cannabinoid CB1and metabotropic GABABreceptors display similar pharmacological effects and co-localize in certain brain regions. In this study, we examined the effects of co-administration of the CB1and GABABantagonists AM251 and baclofen, respectively, on LTP induction in the rat dentate gyrus (DG). Male Wistar rats were anesthetized with urethane. A stimulating electrode was placed in the lateral perforant path (PP), and a bipolar recording electrode was inserted into the DG until maximal field excitatory postsynaptic potentials (fEPSPs) were observed. LTP was induced in the hippocampal area by high-frequency stimulation (HFS) of the PP. fEPSPs and population spikes (PS) were recorded at 5, 30, and 60min after HFS in order to measure changes in the synaptic responses of DG neurons. Our results showed that HFS coupled with administration of AM251 and baclofen increased both PS amplitude and fEPSP slope. Furthermore, co-administration of AM251 and baclofen elicited greater increases in PS amplitude and fEPSP slope. The results of the present study suggest that CB1receptor activation in the hippocampus mainly modifies synapses onto GABAergic interneurons located in the DG. Our results further suggest that, when AM251 and baclofen are administered simultaneously, AM251 can alter GABA release and thereby augment LTP through GABABreceptors. These results suggest that functional crosstalk between cannabinoid and GABA receptors regulates hippocampal synaptic plasticity.
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Masoumeh
M
Nazari
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran. Electronic address: alirezakomaki@gmail.com.
Alireza
A
Komaki
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Iraj
I
Salehi
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Abdolrahman
A
Sarihi
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Siamak
S
Shahidi
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Hamidreza
H
Komaki
Neurophysiology Research Center, Hamadan University of Medical Sciences, Hamadan, Iran.
Ahmad
A
Ganji
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology*; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004347:Drug Interactions; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D058786:GABA-B Receptor Agonists / Q000494:pharmacology*; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008839:Microelectrodes; D010880:Piperidines / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology*; D011897:Random Allocation; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D055366:Synaptic Potentials / Q000187:drug effects / Q000502:physiology; D014520:Urethane / Q000494:pharmacology
D018686:Anesthetics, Intravenous; D063387:Cannabinoid Receptor Antagonists; C543264:Cnr1 protein, rat; D058786:GABA-B Receptor Agonists; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D018080:Receptors, GABA-B; C103505:AM 251; D014520:Urethane; D001418:Baclofen
AM251; Baclofen; Cannabinoid; GABA(B); GABAergic; Long-term potentiation