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Neonatal DSP-4 treatment modifies antinociceptive effects of the CB1 receptor agonist methanandamide in adult rats.

Korossy-Mruk E, Kuter K, Nowak P, Szkilnik R, Rykaczewska-Czerwinska M, Kostrzewa RM, Brus R - Neurotox Res (2012)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Chair and Department of Pharmacology, Medical University of Silesia, H. Jordana 38, 41-808 Zabrze, Poland.

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.

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Effect of neonatal DSP-4 lesioning (50 mg/kg sc on the 1st and 3rd days of postnatal life) on the content of monoamines and their metabolites in frontal cortex (a), thalamus (b) and spinal cord (c), following acute methanandamide (10 mg/kg ip) treatment of adult rats (x ± SEM; n = 6). Legend White square control, Light grey square DSP-4 control + methanandamide, Dark grey square DSP-4 + methanandamide, *P < 0.05, control versus DSP-4, #P < 0.05, control + methanandamide versus DSP-4 + methanandamide, ^P < 0.05, DSP-4 versus DSP-4 + methanandamide
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Fig1: Effect of neonatal DSP-4 lesioning (50 mg/kg sc on the 1st and 3rd days of postnatal life) on the content of monoamines and their metabolites in frontal cortex (a), thalamus (b) and spinal cord (c), following acute methanandamide (10 mg/kg ip) treatment of adult rats (x ± SEM; n = 6). Legend White square control, Light grey square DSP-4 control + methanandamide, Dark grey square DSP-4 + methanandamide, *P < 0.05, control versus DSP-4, #P < 0.05, control + methanandamide versus DSP-4 + methanandamide, ^P < 0.05, DSP-4 versus DSP-4 + methanandamide

Mentions: In rats treated on the 1st and 3rd days of postnatal life with DSP-4 (50 mg/kg sc), and killed at 10 weeks, the adulthood level of NE in the frontal cortex and spinal cord either after saline or methanandamide (10 mg/kg ip) treatment was significantly decreased in comparison to the respective control. DA content in the frontal cortex was reduced in the DSP-4 group while DOPAC and HVA were reduced in spinal cord, versus control. The endogenous level of 5-HT and 5-HIAA in both structures remained unaltered (Fig. 1a, c).Fig. 1


Neonatal DSP-4 treatment modifies antinociceptive effects of the CB1 receptor agonist methanandamide in adult rats.

Korossy-Mruk E, Kuter K, Nowak P, Szkilnik R, Rykaczewska-Czerwinska M, Kostrzewa RM, Brus R - Neurotox Res (2012)

Effect of neonatal DSP-4 lesioning (50 mg/kg sc on the 1st and 3rd days of postnatal life) on the content of monoamines and their metabolites in frontal cortex (a), thalamus (b) and spinal cord (c), following acute methanandamide (10 mg/kg ip) treatment of adult rats (x ± SEM; n = 6). Legend White square control, Light grey square DSP-4 control + methanandamide, Dark grey square DSP-4 + methanandamide, *P < 0.05, control versus DSP-4, #P < 0.05, control + methanandamide versus DSP-4 + methanandamide, ^P < 0.05, DSP-4 versus DSP-4 + methanandamide
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3526738&req=5

Fig1: Effect of neonatal DSP-4 lesioning (50 mg/kg sc on the 1st and 3rd days of postnatal life) on the content of monoamines and their metabolites in frontal cortex (a), thalamus (b) and spinal cord (c), following acute methanandamide (10 mg/kg ip) treatment of adult rats (x ± SEM; n = 6). Legend White square control, Light grey square DSP-4 control + methanandamide, Dark grey square DSP-4 + methanandamide, *P < 0.05, control versus DSP-4, #P < 0.05, control + methanandamide versus DSP-4 + methanandamide, ^P < 0.05, DSP-4 versus DSP-4 + methanandamide
Mentions: In rats treated on the 1st and 3rd days of postnatal life with DSP-4 (50 mg/kg sc), and killed at 10 weeks, the adulthood level of NE in the frontal cortex and spinal cord either after saline or methanandamide (10 mg/kg ip) treatment was significantly decreased in comparison to the respective control. DA content in the frontal cortex was reduced in the DSP-4 group while DOPAC and HVA were reduced in spinal cord, versus control. The endogenous level of 5-HT and 5-HIAA in both structures remained unaltered (Fig. 1a, c).Fig. 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Chair and Department of Pharmacology, Medical University of Silesia, H. Jordana 38, 41-808 Zabrze, Poland.

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.

Show MeSH
Related in: MedlinePlus