title: Neonatal DSP-4 treatment modifies antinociceptive effects of the CB1 receptor agonist methanandamide in adult rats.
abstract: To study the influence of the central noradrenergic system on antinociceptive effects mediated by the CB(1)-receptor agonist methanandamide, intact rats were contrasted with rats in which noradrenergic nerves were largely destroyed shortly after birth with the neurotoxin DSP-4 [N-(-2-chloroethyl)-N-ethyl-2-bromobenzylamine (50 mg/kg sc × 2, P1 and P3); zimelidine (10 mg/kg sc, 30 min pretreatment, selective serotonin reuptake inhibitor). When rats attained 10 weeks of age, monoamine and their metabolite concentrations were determined in the frontal cortex, thalamus, and spinal cord by an HPLC/ED method. Antinociceptive effects after methanandamide (10 mg/kg ip) apply were evaluated by a battery of tests. In addition, immunohistochemistry and densitometric analysis of the cannabinoid CB(1) receptor in the rat brain was performed. DSP-4 lesioning was associated with a reduction in norepinephrine content of the frontal cortex (>90 %) and spinal cord (>80 %) with no changes in the thalamus. Neonatal DSP-4 treatment produced a significant reduction in the antinociceptive effect of methanandamide in the tail-immersion test, hot-plate test and writhing tests. In the paw pressure and formalin hind paw tests results were ambiguous. These findings indicate that the noradrenergic system exerts a prominent influence on analgesia acting via the cannabinoid system in brain, without directly altering CB(1) receptor density in the brain.
authors.affiliation: Chair and Department of Pharmacology, Medical University of Silesia, H. Jordana 38, 41-808 Zabrze, Poland.
authors.forename: Eva
authors.initials: E
authors.lastname: Korossy-Mruk
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Kuter
authors.forename: Przemysław
authors.initials: P
authors.lastname: Nowak
authors.forename: Ryszard
authors.initials: R
authors.lastname: Szkilnik
authors.forename: Monika
authors.initials: M
authors.lastname: Rykaczewska-Czerwinska
authors.forename: Richard M
authors.initials: RM
authors.lastname: Kostrzewa
authors.forename: Ryszard
authors.initials: R
authors.lastname: Brus
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001095:Arachidonic Acids / Q000494:pharmacology*; D001596:Benzylamines / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009498:Neurotoxins / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects* / Q000379:methods; D051381:Rats; D017208:Rats, Wistar; D043884:Receptor, Cannabinoid, CB1 / Q000819:agonists* / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D000700:Analgesics; D001095:Arachidonic Acids; D001596:Benzylamines; D009498:Neurotoxins; D043884:Receptor, Cannabinoid, CB1; C088155:methanandamide; C012102:DSP 4