O antagonista seletivo dopaminérgico D² sulpirida, no córtex pré-frontal medial reduz os prejuízos do etanol sobre a memória operacional de ratos

• Autor(a) principal: Benevides, Marcelo Campos de Almeida
• Data de Publicação: 2007
• Tipo de documento: Dissertação
• Idioma: por
• Título da fonte: Repositório Institucional da Universidade Federal do Espírito Santo (riUfes)
• Texto Completo: http://repositorio.ufes.br/handle/10/7946
• topic: Córtex pré-frontal medial; Sistema dopaminérgico; Etanol; Memória operacional; Labirinto radial; Sulpirida; Fisiologia; 612

The prefrontal córtex (PFC) has been considered as the anatomical site for working memory processing. Its medial portion (mPFC) is part of a brain reward circuitry, essentially mediated by the dopaminergic mesocorticolimbic pathway. The present study examined the involvement of dopaminergic D2 receptors in the mPFC, by means of a selective antagonist of D2 receptors, sulpiride, in the disruptive effects of ethanol (ETOH) on long-term spatial working memory measured by 1-h delayed task performance in an 8-arm radial maze. Male Wistar rats (n=26, 210-270g, ≅ 3 months of age), previously trained in the 8-arm radial maze and with bilateral cannulae implanted in the mPFC (B: + 2.5 mm A, +/- 1 mm L, 2.0 mm V), received intracortical (IC) administration of sulpiride in two different experiments: in the first experiment, 11 animals received IC administration of different doses of sulpiride (0.32, 1.0 or 3.2 µg) or chloride acid 0,05M (HCl) 10 minutes before IC administration of saline (SAL) or ETOH 100 µg. Five minutes after the second administration, animals were submitted to the 1-h delayed task in the radial maze. In the second experiment, 22 animals received IC infusions of sulpiride 1 µg or HCl 0,05 M directly in the mPFC once a day for 4 consecutive days. After the last (4th) administration, animals received acute IC administration of SAL or ETOH 100 µg in the 3rd day, followed by 4-days intervals (days 7, 11 and 15), and tested in 1-h delayed task in the radial maze, after a 5 minutes interval. ETOH IC with previous administration of HCl or sulpiride (3.2 µg) IC yielded significantly larger (p < 0.01) number of errors as compared to the combination of HCl and SAL. Animals treated with lower doses of sulpiride (0.32 µg or 1 µg) combined with ETOH showed significantly (p < 0.01 and p < 0.05, respectively) smaller number of errors as compared to the combination of HCl and ETOH (100 µg) and of sulpiride (3.2 µg) and ETOH (100 µg) in the 1-h post-delay performance. Previous repeated administration of sulpiride into the mPFC did not affect substantially the disruptive effects of ETOH on spatial working memory over the 15 days period, but it significantly reduced the ETOH disruptive effect after the latency of 15 days, suggesting that reduced dopaminergic D2 receptors in the mPFC could change the effects of ETOH in the mPFC. Taken all together, these results suggest the involvement of the dopaminergic system, more specifically the D2 dopaminergic receptors, in ethanol effects on spatial working memory in the mPFC.