RESUMO
Nur-related 1 (Nurr1) and nerve growth factor inducible-B (NGFI-B) constitute closely related subgroups of the nuclear receptor superfamily. One to three hours after 4 mg/kg acute methamphetamine (METH) administration, the levels of Nurr1 mRNA were significantly higher in the prelimbic (PrL), primary motor (M1) and primary somatosensory (S1) cortices and ventral tegmental area (VTA), as compared with the basal level. Pretreatment with 0.5 mg/kg of SCH23390 prevented the acute METH-induced increase in Nurr1 mRNA levels in these brain regions. One to three hours after 4-mg/kg acute METH administration, the levels of NGFI-B mRNA increased significantly in the PrL, M1, S1, striatum, and nucleus accumbens core (AcbC). Pretreatment with either 0.5 mg/kg of MK-801 or 0.5 mg/kg of SCH23390 prevented the acute METH-induced increase in NGFI-B mRNA levels in these brain regions. The levels of mRNAs were determined 3 h after a challenge injection of either saline or 4 mg/kg METH at the three-week withdrawal point in rats which had previously been exposed to either saline or METH (4 mg/kg/day) for 2 weeks. After the saline challenge, the group chronically exposed to METH displayed significantly higher levels of Nurr1 mRNA in the PrL, S1 and VTA, and of NGFI-B mRNA in the PrL, M1, S1, striatum and AcbC than did the group chronically treated with saline. The groups chronically exposed to METH failed to increase Nurr1 mRNA in the VTA, and NGFI-B mRNA in the AcbC, when challenged with 4 mg/kg METH. These results suggest that Nurr1 and NGFI-B mRNA play differential roles upon exposure to METH.
Assuntos
Estimulantes do Sistema Nervoso Central/farmacologia , Proteínas de Ligação a DNA/genética , Expressão Gênica/efeitos dos fármacos , Metanfetamina/farmacologia , RNA Mensageiro/metabolismo , Receptores de Esteroides/genética , Fatores de Transcrição/genética , Análise de Variância , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Proteínas de Ligação a DNA/metabolismo , Masculino , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares , Membro 2 do Grupo A da Subfamília 4 de Receptores Nucleares , Ratos , Ratos Sprague-Dawley , Receptores de Esteroides/metabolismo , Fatores de Tempo , Fatores de Transcrição/metabolismoRESUMO
The effects of acute and chronic administration of methamphetamine (METH) on mRNA levels of synaptotagmin IV (SytIV) and an isoform of synaptic-associated protein of 25 KDa (SNAP25a) have been investigated in rat brain using in situ hybridization. Pretreatment with 0.5 mg/kg dopamine D1 receptor antagonist (SCH23390), but not 0.5 mg/kg N-methyl-D-aspartate (NMDA) receptor antagonist (MK-801), significantly attenuated the increased SytIV mRNA levels induced by acute METH administration in the striatum and the nucleus accumbens. Pretreatment with 0.5 mg/kg SCH23390, but not 0.5 mg/kg MK-801, significantly attenuated the increased SNAP25a mRNA levels induced by acute METH administration in the striatum and the dentate gyrus of the hippocampus. In the chronic treatment experiment, the SytIV mRNA levels of the group that received chronic treatment with METH followed by a METH challenge showed an increase similar to that seen after acute METH administration. In addition, those in the striatum, nucleus accumbens, and dentate gyrus were significantly higher than those of the group that received chronic treatment with saline followed by a METH challenge. The SNAP25a mRNA levels of the group that received chronic treatment with METH followed by a saline challenge were significantly higher than those of the group that received chronic treatment with saline followed by a saline challenge in the striatum and nucleus accumbens. The results of the present study suggest that SytIV may play an important role in the synaptic plasticity underlying METH-induced neuroadaptive changes including behavioral sensitization.
