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It has been hypothesized that spinal morphine tolerance results from protein kinase C (PKC) mediated phosphorylation. Chronic lumbar intrathecal (i.t.) infusion of morphine (20 nmol/μl/h) was shown to produce antinociception on day 1 (d1) that disappeared by d5 (tolerance). On d6, a bolus i.t. probe dose of morphine (60 nmol) produced a more profound antinociception in saline-infused rats than in...
Systemic l-N G -nitroarginine methyl ester or l-NAME (LN), a nitric oxide synthase inhibitor, has been reported to attenuate systemic opioid tolerance and withdrawal. Intrathecal co-administration of LN (100 and 500 nmol/μl per h) with spinal morphine produced only a small diminishing attenuation of tolerance and attenuated only one of seven signs of withdrawal. These results show that LN...
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