RESUMEN
We have previously shown strain and dose differences in heroin-induced behavior, reward and regional expression of somatostatin receptor mRNAs in C57BL/6J and 129P3/J mice. Using Real Time PCR we examined the effects of five doses of heroin on the levels of the transcripts of endogenous opioid peptides and their receptors and dopaminergic receptors in the mesocorticolimbic and nigrostriatal pathways in these same mice. Compared to C57BL/6J animals, 129P3/J mice had higher mRNA levels of Oprk1 in the nucleus accumbens and of Oprd1 in the nucleus accumbens and a region containing both the substantia nigra and ventral tegmental area (SN/VTA). In the cortex of 129P3/J mice, lower levels of both Oprk1 and Oprd1 mRNAs were observed. Pdyn mRNA was also lower in the caudate putamen of 129P3/J mice. Strain differences were not found in the levels of Oprm1, Penk or Pomc mRNAs in any region examined. Within strains, complex patterns of heroin dose-dependent changes in the levels of Oprm1, Oprk1 and Oprd1 mRNAs were observed in the SN/VTA. Additionally, Oprd1 mRNA was dose-dependently elevated in the hypothalamus. Also in the hypothalamus, we found higher levels of Drd1a mRNA in C57BL/6J mice than in 129P3/J animals and higher levels of DAT (Slc6a3) mRNA in the caudate putamen of C57BL/6J animals than in 129P3/J counterparts. Heroin had dose-related effects on Drd1a mRNA in the hypothalamus and on Drd2 mRNA in the caudate putamen.
Asunto(s)
Química Encefálica/genética , Regulación de la Expresión Génica , Heroína/farmacología , ARN Mensajero/biosíntesis , Animales , Química Encefálica/efectos de los fármacos , Masculino , Ratones , Ratones de la Cepa 129 , Ratones Endogámicos C57BL , ARN Mensajero/genética , Receptores Opioides delta/agonistas , Receptores Opioides delta/genética , Receptores Opioides kappa/agonistas , Receptores Opioides kappa/genética , Receptores Opioides mu/agonistas , Receptores Opioides mu/genética , Especificidad de la EspecieRESUMEN
Acute injections of 8mg/kg of 3,4-dihydroxy-l-phenylalanine (l-DOPA) or 0.05mg/kg rimonabant equally improved contralateral forepaw stepping in rats with unilateral 6-hydroxydopamine (6-OHDA) lesions, and their combination improved stepping more than either drug alone. However, 0.05mg/kg rimonabant did not alter the changes in stepping produced by acute injections of a dyskinesic dose of 35mg/kg l-DOPA. Thus, not only is a cannabinoid antagonist monotherapeutic in this animal model of Parkinson's disease, but it also enhances the therapeutic effect of a moderate, but not a high, dose of l-DOPA.
