RESUMO
The 5-lipoxygenase/leukotriene system has been implicated in both physiological and pathological states within the central nervous system. Understanding how this system interacts with the dopaminergic system could provide valuable insights into dopamine-related pathologies. This study focused on examining both motor and non-motor dopamine-related responses in 5-lipoxygenase/leukotriene-deficient mice. We used pharmacological agents such as amphetamine, apomorphine, and reserpine to challenge the dopaminergic system, evaluating their effects on prepulse inhibition reaction (PPI), general motor activity, and oral involuntary movements. Additionally, we analyzed striatal glial marker expression (GFAP and Iba-1) in reserpine-treated mice. The 5-lipoxygenase/leukotriene-deficient mice exhibited increased spontaneous locomotor activity, including both horizontal and vertical exploration, along with stereotyped behavior compared to wild-type mice. This hyperactivity was reduced by acute apomorphine treatment. Although basal PPI responses were unchanged, 5-lipoxygenase/leukotriene-deficient mice displayed a significant reduction in susceptibility to amphetamine-induced PPI disruption. Conversely, these mice were more vulnerable to reserpine-induced involuntary movements. There were no significant differences in the basal expression of striatal GFAP and Iba-1 positive cells between 5-lipoxygenase/leukotriene-deficient and wild-type mice. However, reserpine treatment significantly increased GFAP immunoreactivity in wild-type mice, an effect not observed in 5-lipoxygenase-deficient mice. Additionally, the percentage of activated microglia was significantly higher in reserpine-treated wild-type mice, an effect absents in 5-lipoxygenase/leukotriene-deficient mice. Our findings suggest that 5-lipoxygenase/leukotriene deficiency leads to a distinctive dopaminergic phenotype, indicating that leukotrienes may influence the modulation of dopamine-mediated responses.
Assuntos
Anfetamina , Araquidonato 5-Lipoxigenase , Dopamina , Animais , Masculino , Camundongos , Anfetamina/farmacologia , Apomorfina/farmacologia , Araquidonato 5-Lipoxigenase/metabolismo , Araquidonato 5-Lipoxigenase/deficiência , Araquidonato 5-Lipoxigenase/genética , Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Ligação ao Cálcio/deficiência , Corpo Estriado/metabolismo , Corpo Estriado/efeitos dos fármacos , Dopamina/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microfilamentos/metabolismo , Atividade Motora/efeitos dos fármacos , Atividade Motora/fisiologia , Inibição Pré-Pulso/efeitos dos fármacos , Inibição Pré-Pulso/fisiologia , Reserpina/farmacologia , Comportamento Estereotipado/efeitos dos fármacosRESUMO
OBJECTIVE AND METHODS: We investigated the locomotor, emotional, physiological, and neurobiological effects induced by low-dose reserpine repeated treatment (0.1 mg/kg; 14 injections) in males from the Lewis (LEW), Spontaneously Hypertensive Rats (SHR), and SHR.LEW-(D4Rat76-D4Mgh11) (SLA16) isogenic rat strains, which have different genetic backgrounds on chromosome 4. Behavioral responses in the catalepsy, open-field, and oral movements' tests were coupled with blood pressure, body weight, and striatal tyrosine hydroxylase (TH) level assessments to establish neurobiological comparisons between reserpine-induced impairments and genetic backgrounds RESULTS: Results revealed the SHR strain was more sensitive in the catalepsy test and exhibited higher TH immunoreactivity in the dorsal striatum. The SLA16 strain presented more oral movements, suggesting increased susceptibility to develop oral dyskinesia. CONCLUSIONS: Our results showed the efficacy of repeated treatment with a low dose of reserpine and demonstrated, for the first time, the genetic influence of a specific region of chromosome 4 on the expression of these effects.