Envolvimento do sistema colinérgico hipocampal no efeito tipo depressivo provocado pela retirada do crack

Abstract

Introduction: Crack, when withdrawn abruptly after repeated administrations, is associated with physical and psychological disorders, such as mental disorders. The hippocampal cholinergic system has been implicated in several pathologies, such as in addiction to drugs of abuse and in anxiety and depression disorders. Objective: Evaluate the involvement of the hippocampal cholinergic system in the behaviors related to anxiety and depression associated with crack withdrawal in Swiss male mice. Material and methods: The nimals were exposed to crack smoke (burning of 200 or 800 mg of crack) once daily for 5 minutes, for 5 consecutive days. After 24 and 48 hours of the last exposure the animals were submitted to tests of anxiety (elevated plus maze; EPM), locomotion (open field, OF) and depression (forced swim test, FST). The hippocampal activity of the enzymes acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was evaluated in one group of animals 24h after the last exposure to crack smoke (200 or 800 mg); while another group of animals, in the same withdrawal period and exposed to only 200 mg of crack, was treated with intra-hippocampal administration with PBS or Pirenzepine (0.06 nmol; selective M1 muscarinic receptor antagonist), and, after 5 min, submitted to FST. Finally, serological levels of corticosterone were evaluated 24 hours and 48 hours after the last exposure to crack smoke (200 mg). Results: Our results showed that 24h or 48h after the last exposure to crack smoke (200 mg, only) there was a reduction in the number of head dipping in the EPM; in the time of 48 hours and in this same amount of crack we found an increase in the percentage of time in the open arms of the EPM. When evaluated 24 hours (200 and 800 mg) or 48 hours (200 mg, only), we found an increase in locomotor activity in the OF and an increase in the time of immobility in the FST. These results taken together indicate that the animals presented a depressive-like behavior, but not anxious. In relation to hippocampal enzymes AChE and BChE, exposure to crack smoke (800 mg, only) decreased the activity of these enzymes. However, this same amount of crack decreased significantly the concentration of total proteins in the hippocampus, indicating a neurotoxic effect of this amount of crack. In addition, administration of pirenzepine was able to reverse the effect of the depressive- like effect triggered 24 hours after the last exposure to crack smoke. Finally, 24h or 48h after the last exposure to crack smoke (200 or 800 mg) animals had increased levels of corticosterone, indicating high levels of stress in animals. Conclusion: Our results indicated that 24 h after the last exposure to crack smoke (200 mg, non-toxic dose) the animals presented a depressive-like behavior – from the activation of M1-muscarinic receptors in the hippocampus and from elevation in serologic levels of corticosterone. In addition, the established experimental protocol will allow better study of the involvement of the hippocampal cholinergic system in the withdrawal of drugs of abuse and associated comorbidities, especially crack and depression, respectively.