Cannabinoid receptor-1 activation suppresses inhibitory synaptic activity in human dentate gyrus.
In spite of their popular uses as recreational drugs and their potential therapeutic uses, little direct information has been obtained about the synaptic effects of cannabinoids in the human brain. In the present study, patch-clamp recordings were performed on granule cells of the human dentate gyrus and the effects of cannabinoid receptor-1 (CB1) activation on inhibitory synaptic activity were examined. Activation of CB1 receptors by WIN55212-2 significantly suppressed both frequency and amplitude of spontaneous inhibitory synaptic currents (IPSCs) to about 50% of control. The suppressive effects were completely abolished in the presence of the CB1 receptor antagonist, AM251. WIN55212-2 also suppressed evoked IPSCs. However, neither frequency nor amplitude of miniature IPSCs were affected by WIN55212-2. These results provide electrophysiological evidence for the role of CB1 receptors in modulating inhibitory activity in human dentate gyrus.
Nakatsuka
Terumasa
T
Department of Oral and Maxilloficial Surgery and Diagnostic Sciences, College of Dentistry, University of Florida, Gainesville, FL 32610, USA.
Chen
Huan-Xin
HX
Roper
Steven N
SN
Gu
Jianguo G
JG
D000293:Adolescent; D000328:Adult; D002186:Cannabinoids / Q000378:metabolism*; D002648:Child; D018891:Dentate Gyrus / Q000187:drug effects* / Q000502:physiology; D004833:Epilepsy, Temporal Lobe / Q000473:pathology; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition; D018408:Patch-Clamp Techniques; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000502:physiology; D013569:Synapses / Q000187:drug effects* / Q000502:physiology
D002186:Cannabinoids; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug