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 CB1-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 CB1 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 CB1 receptor density in the brain.

Antinociceptive Effects of H3 (R-Methylhistamine) and GABAB (Baclofen)-Receptor Ligands in an Orofacial Model of Pain in Rats

“…The instrumentation included an electrochemical detector (Gilson, Villiers-le-Bel, France) model 141 with flow cell, piston pump model 302 with head 5SC (Gilson, Villiers-le-Bel, France), manometric module model 802 (Gilson, Villiers-le-Bel, France), thermostat for STH 595 column (Dionex Softron Gmbh, Germering, Germany), precolumn Hypersil BDS C18, 10 × 4 mm, 3 μm (ThermoQuest, Waltham, GB) and chromatographic column Hypersil BDS C18, 250 × 4.6 mm, 3 μm (ThermoQuest, Waltham, GB). The data were quantified using the area under the peaks and external standards, using Chromeleon software (Dionex, Germany) (Nowak et al 2006; Korossy-Mruk et al 2013). …”