Electrophysiologic effects of systemic and locally infused epibatidine on locus coeruleus neurons.
We evaluated the electrophysiologic response of locus coeruleus neurons to the systemic and local infusion of epibatidine. Rats were anesthetized with 2% halothane and single-unit locus coeruleus discharge was recorded after administration of systemic (2.5, 5 and 10 microg/kg subcutaneously) and intracoerulear (0.03-0.01-0.001 microg) epibatidine. The subcutaneous epibatidine activated locus coeruleus neurons only at the highest dose (10 microg/kg). The 2.5-5 microg/kg doses, previously shown to induce analgesia, did not activate locus coeruleus neurons. The intracoerulear infusion of epibatidine induced excitement of locus coeruleus neurons at every tested dose. Higher doses (0.03 and 0.01 microg) excited 100% of the recorded neurons. A significantly lower number of neurons (50% and 43% respectively) were excited when lower doses (0.005-0.001 microg) were used (P=0.035). The intracoerulear infusion of mecamylamine (1 microg) significantly reduced neuronal discharge rate (45%) and blocked the effects of epibatidine. The intra-dorsal raphe infusion of 0.03 microg epibatidine induced significant excitation of locus coeruleus neurons. These data show that the administration of epibatidine induces excitation of locus coeruleus neurons, which is mediated by nicotinic receptors. This activation occurs after systemic and selective local administration of epibatidine. The response of locus coeruleus neurons to systemic and locally administered epibatidine is dose-related.
Ganesh
Arjunan
A
Department of Anesthesia and Critical Care of Medicine, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Gonzalez-Sulser
Alfredo
A
Chaijale
Nayla
N
Cucchiaro
Giovanni
G
D000200:Action Potentials; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D007263:Infusions, Parenteral; D007279:Injections, Subcutaneous; D008125:Locus Coeruleus / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D011725:Pyridines / Q000008:administration & dosage*; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D008464:Mecamylamine; C082748:epibatidine