benzofurans and arachidonylcyclopropylamide

Cannabinoids modulate inhibitory GABAergic neurotransmission in many brain regions. Within the temporal lobe, cannabinoid receptors are highly expressed, and are located presynaptically at inhibitory terminals. Here, we have explored the role of type-1 cannabinoid receptors (CB1Rs) at the level of inhibitory synaptic currents and field-recorded network oscillations. We report that arachidonylcyclopropylamide (ACPA; 10 microM), an agonist at CB1R, inhibits GABAergic synaptic transmission onto both superficial and deep medial entorhinal (mEC) neurones, but this has little effect on network oscillations in beta/gamma frequency bands. By contrast, the CB1R antagonist/inverse agonist LY320135 (500 nM), increased GABAergic synaptic activity and beta/gamma oscillatory activity in superficial mEC, was suppressed, whilst that in deep mEC was enhanced. These data indicate that cannabinoid-mediated effects on inhibitory synaptic activity may be constitutively active in vitro, and that modulation of CB1R activation using inverse agonists unmasks complex effects of CBR function on network activity.

Topics: Analysis of Variance; Animals; Arachidonic Acids; Benzofurans; Beta Rhythm; Entorhinal Cortex; gamma-Aminobutyric Acid; In Vitro Techniques; Inhibitory Postsynaptic Potentials; Male; Nerve Net; Neural Inhibition; Neurons; Patch-Clamp Techniques; Presynaptic Terminals; Rats; Rats, Wistar; Receptor, Cannabinoid, CB1; Statistics, Nonparametric; Synaptic Transmission