CB1 cannabinoid receptors inhibit the glutamatergic component of KCl-evoked excitation of locus coeruleus neurons in rat brain slices

CB1 cannabinoid receptors located at presynaptic sites suppress synaptic transmission in the rat brain. The aim of this work was to examine by single-unit extracellular techniques the effect of the synthetic cannabinoid receptor agonist WIN 55212-2 on KCl-evoked excitation of locus coeruleus neurons in rat brain slices. Short applications of KCl (30 mM) increased by 9-fold the firing rate of locus coeruleus cells. Perfusion with the GABAA receptor antagonist picrotoxin (100 μM) increased KCl-evoked effect, whereas NMDA and non-NMDA glutamate receptor antagonists (D-AP5 100 μM and CNQX 30 μM, respectively) were able to decrease KCl-evoked effect only in the presence of picrotoxin (100 μM). Bath application of WIN 55212-2 (10 μM) inhibited KCl-evoked effect; this inhibition was blocked by the CB1 receptor antagonist AM 251 (1 μM). However, a lower concentration of WIN 55212-2 (1 μM) did not significantly change KCl effect. In the presence of picrotoxin (100 μM), perfusion with D-AP5 (100 μM) or CNQX (30 μM) blocked WIN 55212-2-induced inhibition, although picrotoxin (100 μM) itself failed to affect cannabinoid effect. In conclusion, GABAergic and glutamatergic components are both involved in KCl-evoked excitation of LC neurons, although CB1 receptors only seem to inhibit the glutamatergic component of KCl effect in the locus coeruleus.