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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 antinociception effects assessed in the formalin test after methanandamide (10 mg/kg ip) treatment in rats (mean ± SEM; n = 8). Legend as in Fig. 3
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Fig7: Effect of neonatal DSP-4 lesioning (50 mg/kg sc on the 1st and 3rd days of postnatal life) on antinociception effects assessed in the formalin test after methanandamide (10 mg/kg ip) treatment in rats (mean ± SEM; n = 8). Legend as in Fig. 3

Mentions: To assess the effect of a neonatal noradrenergic lesion on adulthood analgesic action of methanandamide, a comparison of DSP-4 and control rats was made for the behavioral responses to sc injection of 50 μl (5 %) of formalin into a hind paw. Methanandamide (10 mg/kg ip) was administered 30 min before formalin application. Both groups showed the typical biphasic nociceptive response for the 60 min of testing, but DSP-4 lesioned rats scored fewer points (spending less time licking/biting the injected hind paw) in the first phase of the formalin test than the control group (P < 0.05 at 1 and 5 min), but in the remaining 50 min of observation the opposite effect was observed (Fig. 7).Fig. 7


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 antinociception effects assessed in the formalin test after methanandamide (10 mg/kg ip) treatment in rats (mean ± SEM; n = 8). Legend as in Fig. 3
© Copyright Policy
Related In: Results  -  Collection

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

Fig7: Effect of neonatal DSP-4 lesioning (50 mg/kg sc on the 1st and 3rd days of postnatal life) on antinociception effects assessed in the formalin test after methanandamide (10 mg/kg ip) treatment in rats (mean ± SEM; n = 8). Legend as in Fig. 3
Mentions: To assess the effect of a neonatal noradrenergic lesion on adulthood analgesic action of methanandamide, a comparison of DSP-4 and control rats was made for the behavioral responses to sc injection of 50 μl (5 %) of formalin into a hind paw. Methanandamide (10 mg/kg ip) was administered 30 min before formalin application. Both groups showed the typical biphasic nociceptive response for the 60 min of testing, but DSP-4 lesioned rats scored fewer points (spending less time licking/biting the injected hind paw) in the first phase of the formalin test than the control group (P < 0.05 at 1 and 5 min), but in the remaining 50 min of observation the opposite effect was observed (Fig. 7).Fig. 7

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