title: CB(1) cannabinoid receptors inhibit the glutamatergic component of KCl-evoked excitation of locus coeruleus neurons in rat brain slices.
abstract: CB(1) 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 GABA(A) receptor antagonist picrotoxin (100 microM) increased KCl-evoked effect, whereas NMDA and non-NMDA glutamate receptor antagonists (D-AP5 100 microM and CNQX 30 microM, respectively) were able to decrease KCl-evoked effect only in the presence of picrotoxin (100 microM). Bath application of WIN 55212-2 (10 microM) inhibited KCl-evoked effect; this inhibition was blocked by the CB(1) receptor antagonist AM 251 (1 microM). However, a lower concentration of WIN 55212-2 (1 microM) did not significantly change KCl effect. In the presence of picrotoxin (100 microM), perfusion with D-AP5 (100 microM) or CNQX (30 microM) blocked WIN 55212-2-induced inhibition, although picrotoxin (100 microM) itself failed to affect cannabinoid effect. In conclusion, GABAergic and glutamatergic components are both involved in KCl-evoked excitation of LC neurons, although CB(1) receptors only seem to inhibit the glutamatergic component of KCl effect in the locus coeruleus.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of the Basque Country, Barrio Sarriena s/n, E-48940 Leioa, Bizkaia, Spain.
authors.forename: Aitziber
authors.initials: A
authors.lastname: Mendiguren
authors.forename: Joseba
authors.initials: J
authors.lastname: Pineda
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D048588:Benzoxazines; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018683:Excitatory Amino Acid Agents / Q000494:pharmacology; D018756:GABA Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D008125:Locus Coeruleus / Q000166:cytology*; D008297:Male; D009025:Morpholines / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009433:Neural Inhibition / Q000187:drug effects*; D009474:Neurons / Q000187:drug effects*; D010852:Picrotoxin / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists / Q000502:physiology*; D013997:Time Factors
chemical_list: D048588:Benzoxazines; D002121:Calcium Channel Blockers; D018683:Excitatory Amino Acid Agents; D018756:GABA Antagonists; D018698:Glutamic Acid; D009025:Morpholines; D009281:Naphthalenes; D010852:Picrotoxin; D010880:Piperidines; D011189:Potassium Chloride; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; C103505:AM 251; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone