Question

For glutamatergic synapses, how would THC actions on presynaptic CB1 receptors on glutamateric axon terminals affect the excitatory transmission typically evoked by activity at those synapses? For GABAergic synapses, how would THC actions on presynaptic CB1 receptors on GABAergic axon terminals affect the inhibitory transmission typically evoked by activity at those synapses?

Answer 1

Hofman and Lupia (2013) reported that prolonged application of THC to cultured hippocampal neurons desensitized CB1 receptors on glutamate terminals, suggesting that THC can antagonize the effects of full agonists at CB1 receptors acutely, but can also effectively down-regulate CB1 receptor function following longer exposure. Furthermore, inhibitory axon terminals are more sensitive to, and more completely inhibited by THC. These lead to a disruption of hippocampal network activity that is largely controlled by synchronized GABA neuron activity and is profoundly disrupted by cannabinoids (Hajos et al. 2000; Robbe et al. 2006)

References:

Hoffman AF, Lupica CR. Synaptic Targets of ?9-Tetrahydrocannabinol in the Central Nervous System. Cold Spring Harbor Perspectives in Medicine. 2013;3(8):a012237. doi:10.1101/cshperspect.a012237.