Resumo

Objective: The objective of the present study was to evaluate the involvement of the indirect pathway, through the intraperitonial and intracranial infusion of quinpirole and sulpiride, in the two-way active avoidance task. Methods: Adult male Wistar rats (n = 107), weighing 280-320 g were used in this experiment. Food and water were supplied ad libitum. Seven days before the initiation of behavioral experiments, the animals had guide-cannula implanted bilaterally (1 cm long, 23 gauge) aimed 2.0mm above the dorsolateral striatum (DLS) or nucleus accumbens (NAc). Each cannula was fixed with polyacrylic cement anchored to the skull with stainless-steel screws and plugged with stainless-steel plugs. After surgery, the animals were allowed to recover from anesthesia in a temperature controlled chamber and then placed in cages. The D2 receptor agonist, quinpirole and the D2 receptor antagonist, sulpiride were dissolved in saline for intraperitonial administration and in artificial LCR for intracranial administration. Quinpirole (0,5 , 0,1 , 0,05 mg/Kg), Sulpiride (1,0 , 0,5 mg/Kg) and vehicle were administered 20 min before training in the two-way active avoidance task. The intra-NAc and the intra-DLS infusions were executed immediately before training session. The animals were gently held and a removable injector was inserted into the guide cannula extending 2 mm beyond the guide tip, and LCR (0,4 µL) or quinpirole (0,4 µg / 0,4 µL) or sulpiride (0,4 µg / 0,4 µL), was infused bilaterally into the DS or NAc. The injector was linked to a 10 μl Hamilton syringe and the volume was injected over 1 min period. The injector was retained in place for an additional minute. The active avoidance test apparatus consisted of a box divides into two compartments by a wall with door that remained open during the tests. In the training session, after 10 min of habituation, 40 light cues (conditioned stimulus: maximum duration of 10 s) were paired with a subsequent 0.5mA footshock (unconditioned stimulus: maximum duration of 10 s) until the animal crossed to the other compartment. The following parameters were registered: number of avoidances, number of escapes, number of non-responses and number of inter-trial-crossings. The test session, conducted 24 h later, was identical to the training one, except for a 5 min habituation time and for the animals not received any drug. Data were analysed by two-way ANOVA followed by Newman-Keuls test and differences were considered significant when p ≤ 0,05. Results: Compared to control groups, the following significant alterations were observed: the intra-NAc administration of sulpiride decreased the number of avoidances in the training and in the test session (F(4,53) = 18,19, p≤0,01); increased the number of non-responses in both sessions (F(4,53) = 16,97, p≤0,01); and decreased the number of inter-trial crossings (F(4,53) = 11,11, p≤0,01). The intra-DLS administration of sulpiride decreased the number of avoidances (F(4,46) = 2,65, p≤0,05) and increased the number of non-responses (F(4,46) = 2,67; p≤0,05). Conclusion: The present results suggest that learning and memory processes of the two-way active avoidance task are impaired by the blockade of the corticostriatal indirect pathway.