Effects of lithium on inflammatory and neurotrophic factors after an immune challenge in a lisdexamfetamine animal model of mania

Abstract

Objective:To evaluate whether an animal model of mania induced by lisdexamfetamine dimesylate (LDX) has an inflammatory profile and whether immune activation by lipopolysaccharides (LPS) has a cumulative effect on subsequent stimuli in this model. We also evaluated the action of lithium (Li) on inflammatory and neurotrophic factors.Methods:Adult male Wistar rats were subjected to an animal model of mania. After the open-field test, they were given LPS to induce systemic immune activation. Subsequently, the animals’ blood was collected, and their serum levels of brain-derived neurotrophic factor and inflammatory markers (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-1β, IL-10, and inducible nitric oxide synthase [iNOS]) were measured.Results:LDX induced hyperactivity in the animals, but no inflammatory marker levels increased except brain-derived neurotrophic factor (BDNF). Li had no effect on serum BDNF levels but prevented iNOS levels from increasing in animals subjected to immune activation.Conclusion:Although Li prevented an LPS-induced increase in serum iNOS levels, its potential anti-inflammatory effects in this animal model of mania were conflicting.

Investigation of Blood-Brain Barrier Disruption in an Animal Model of Mania Induced by d-Amphetamine

“…However, no changes in TNFα levels were found in the serum and brain regions analyzed in our model. Still, no differences in in ammatory cytokines levelssuch as TNFα, IL-1β, and IL-10 -have been previously described in rodents injected with AMPH or its derivates (Bristot et al, 2019;Gubert et al, 2016).…”

Transcriptome Changes in Three Brain Regions during Chronic Lithium Administration in the Rat Models of Mania and Depression

“…Moreover, these behaviors were reversed by the administration of mood stabilizers, including lithium [ 40 , 43 ]. This chronic amphetamine-induced mania model showed recently good face, predictive and construct validity in modeling mania in Wistar rats [ 44 , 45 , 46 , 47 ].…”

Andrographolide blocks 50-kHz ultrasonic vocalizations, hyperlocomotion and oxidative stress in an animal model of mania

“…LDX is a long-acting pro-drug of d-amphetamine employed in the therapeutic management of attention deficit/hyperactivity disorder (Ermer et al, 2016). LDX administration has also been used to mimic manic-like behavior in animals (Macêdo et al, 2013;de Souza et al, 2015;Eger et al, 2016;Wendler et al, 2016;Ascoli et al, 2017;Bristot et al, 2019). These manic-like behaviors were reversed or prevented by treatment with lithium or valproate (Macêdo et al, 2013;de Souza et al, 2015;Wendler et al, 2016;Ascoli et al, 2017;Bristot et al, 2019).…”

“…More recently, we proposed that 50-kHz ultrasonic vocalizations (USV), which are related to positive affect, could be an additional readout for manic-like states (Pereira et al, 2014;Wendler et al, 2016Wendler et al, , 2019Engelhardt et al, 2017). In this line, lisdexamfetamine (LDX), a pro-drug of amphetamine, induces increased locomotor activity and 50-kHz USV that are prevented by lithium or valproate administration (Macêdo et al, 2013;de Souza et al, 2015;Wendler et al, 2016;Bristot et al, 2019). According to their spectrogram shapes, 50-kHz USV can be classified into different subtypes (Costa et al, 2020;Mulvihill and Brudzynski, 2020;Wright et al, 2010) and we have applied a rather common classification into four subtypes: trill, step, mixed and flat (e.g.…”