Pharmacology, biochemistry, and behavior
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Pharmacol. Biochem. Behav. · Jun 2009
Differences in basal and morphine-induced FosB/DeltaFosB and pCREB immunoreactivities in dopaminergic brain regions of alcohol-preferring AA and alcohol-avoiding ANA rats.
Besides alcohol, alcohol-preferring AA and alcohol-avoiding ANA rats differ also with respect to other abused drugs. To study the molecular basis of these differences, we examined the expression of two transcription factors implicated in addiction, DeltaFosB and pCREB, in brain dopaminergic regions of AA and ANA rats. The effects of morphine and nicotine were studied to relate the behavioral and molecular changes induced by these drugs. ⋯ The enhanced nicotine-induced locomotor sensitization found in AA compared with ANA rats seems to depend in addition to dopamine and DeltaFosB on other mechanisms. These findings suggest that enhanced sensitivity of AA rats to morphine is related to augmented morphine-induced expression of FosB/DeltaFosB and morphine-induced reduction of pCREB levels. Moreover, altered innate expression of FosB/DeltaFosB and pCREB in AA rats is likely to affect the sensitivity of these rats to abused drugs.
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Pharmacol. Biochem. Behav. · Jun 2009
Synergistic antinociception of intrathecal sildenafil with clonidine in the rat formalin test.
Spinal sildenafil (phosphodiesterase 5 inhibitor) and clonidine (alpha-2 adrenoceptor agonist) have shown antinociception. The author examined the properties of drug interaction after concurrent administration of intrathecal sildenafil-clonidine, and further clarified the reciprocity of sildenafil and clonidine. Catheters were inserted into the intrathecal space of male Sprague-Dawley rats. ⋯ These results suggest that sildenafil and clonidine, and the mixture of the two are effective against acute pain and facilitated pain state at the spinal level. Furthermore, synergism was noted after delivery of sildenafil-clonidine mixture. The antinociception of sildenafil can be modulated by spinal alpha-2 adrenoceptor, while the effect of clonidine is independent on the guanyly cyclase.