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Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania.
J Psychiatry Neurosci 2006; 31(5):326-32JP

Abstract

OBJECTIVE

Previous studies have suggested that oxidative stress may play a role in the pathophysiology of bipolar disorder (BD). Moreover, recent studies indicate that lithium and valproate exert neuroprotective effects against oxidative stress. We studied the effects of the mood stabilizers lithium and valproate on amphetamine-induced oxidative stress in an animal model of mania.

METHODS

In the first model (reversal treatment), adult male Wistar rats received d-amphetamine or saline for 14 days, and between the 8th and 14th days, they were treated with lithium, valproate or saline. In the second model (prevention treatment), rats were pretreated with lithium, valproate or saline, and between the 8th and 14th days, they received d-amphetamine or saline. We assessed locomotor activity with the open-field task. We measured thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation, as parameters of oxidative stress, and superoxide dismutase (SOD) and catalase (CAT), the major antioxidant enzymes, in the prefrontal cortex and hippocampus.

RESULTS

Lithium and valproate reversed (reversal treatment model) and prevented (prevention treatment model) amphetamine-induced hyperactivity and reversed and prevented amphetamine-induced TBARS formation in both experiments. However, the co-administration of lithium or valproate with amphetamine increased lipid peroxidation, depending on the brain region and treatment regimen. No changes in protein carbonyl formation were observed. SOD activity varied with different treatment regimens, and CAT activity increased when the index of lipid peroxidation was more robust.

CONCLUSION

Our findings suggest that lithium and valproate exert protective effects against amphetamine-induced oxidative stress in vivo, further supporting the hypothesis that oxidative stress may be associated with the pathophysiology of BD.

Authors+Show Affiliations

Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, and the Bipolar Disorders Program, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16951735

Citation

Frey, Benicio N., et al. "Effects of Lithium and Valproate On Amphetamine-induced Oxidative Stress Generation in an Animal Model of Mania." Journal of Psychiatry & Neuroscience : JPN, vol. 31, no. 5, 2006, pp. 326-32.
Frey BN, Valvassori SS, Réus GZ, et al. Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania. J Psychiatry Neurosci. 2006;31(5):326-32.
Frey, B. N., Valvassori, S. S., Réus, G. Z., Martins, M. R., Petronilho, F. C., Bardini, K., ... Quevedo, J. (2006). Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania. Journal of Psychiatry & Neuroscience : JPN, 31(5), pp. 326-32.
Frey BN, et al. Effects of Lithium and Valproate On Amphetamine-induced Oxidative Stress Generation in an Animal Model of Mania. J Psychiatry Neurosci. 2006;31(5):326-32. PubMed PMID: 16951735.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of lithium and valproate on amphetamine-induced oxidative stress generation in an animal model of mania. AU - Frey,Benicio N, AU - Valvassori,Samira S, AU - Réus,Gislaine Z, AU - Martins,Márcio R, AU - Petronilho,Fabrícia C, AU - Bardini,Katrine, AU - Dal-Pizzol,Felipe, AU - Kapczinski,Flávio, AU - Quevedo,João, PY - 2006/9/5/pubmed PY - 2006/11/11/medline PY - 2006/9/5/entrez SP - 326 EP - 32 JF - Journal of psychiatry & neuroscience : JPN JO - J Psychiatry Neurosci VL - 31 IS - 5 N2 - OBJECTIVE: Previous studies have suggested that oxidative stress may play a role in the pathophysiology of bipolar disorder (BD). Moreover, recent studies indicate that lithium and valproate exert neuroprotective effects against oxidative stress. We studied the effects of the mood stabilizers lithium and valproate on amphetamine-induced oxidative stress in an animal model of mania. METHODS: In the first model (reversal treatment), adult male Wistar rats received d-amphetamine or saline for 14 days, and between the 8th and 14th days, they were treated with lithium, valproate or saline. In the second model (prevention treatment), rats were pretreated with lithium, valproate or saline, and between the 8th and 14th days, they received d-amphetamine or saline. We assessed locomotor activity with the open-field task. We measured thiobarbituric acid reactive substances (TBARS) and protein carbonyl formation, as parameters of oxidative stress, and superoxide dismutase (SOD) and catalase (CAT), the major antioxidant enzymes, in the prefrontal cortex and hippocampus. RESULTS: Lithium and valproate reversed (reversal treatment model) and prevented (prevention treatment model) amphetamine-induced hyperactivity and reversed and prevented amphetamine-induced TBARS formation in both experiments. However, the co-administration of lithium or valproate with amphetamine increased lipid peroxidation, depending on the brain region and treatment regimen. No changes in protein carbonyl formation were observed. SOD activity varied with different treatment regimens, and CAT activity increased when the index of lipid peroxidation was more robust. CONCLUSION: Our findings suggest that lithium and valproate exert protective effects against amphetamine-induced oxidative stress in vivo, further supporting the hypothesis that oxidative stress may be associated with the pathophysiology of BD. SN - 1180-4882 UR - https://www.unboundmedicine.com/medline/citation/16951735/Effects_of_lithium_and_valproate_on_amphetamine_induced_oxidative_stress_generation_in_an_animal_model_of_mania_ L2 - http://www.jpn.ca/vol31-issue5/31-5-326/ DB - PRIME DP - Unbound Medicine ER -