HIV antiretroviral drug Efavirenz induces anxiety-like and depression-like behavior in rats: evaluation of neurotransmitter alterations in the striatum

Cavalcante, Giuliana Ignácio Teixeira; Filho, Adriano José Maia Chaves; Linhares, Maria Isabel; Lima, Camila Nayane de Carvalho; Venâncio, Edith Teles; Rios, Emiliano Ricardo Vasconcelos; Souza, Francisca C. F.; Vasconcelos, Silvânia Maria Mendes; Macêdo, Danielle Silveira; Fonteles, Marta Maria de França

doi:10.1016/j.ejphar.2017.02.009

Cited by 21 publications

(22 citation statements)

References 45 publications

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“…It was reported that levels of amino acid neurotransmitters such as Glu (an excitatory neurotransmitter) and GABA (an inhibitory neurotransmitter) are related to behavior [ 33 , 34 , 35 ], especially the emotional behavior [ 36 ]. In addition, the ratio of Glu to GABA [ 37 ] and the activity of AchE [ 38 , 39 ] were reported to play an important role in learning and memory ability.…”

Section: Discussionmentioning

confidence: 99%

Effects of 1.8 GHz Radiofrequency Fields on the Emotional Behavior and Spatial Memory of Adolescent Mice

Zhang

Guo

et al. 2017

IJERPH

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The increasing use of mobile phones by teenagers has raised concern about the cognitive effects of radiofrequency (RF) fields. In this study, we investigated the effects of 4-week exposure to a 1.8 GHz RF field on the emotional behavior and spatial memory of adolescent male mice. Anxiety-like behavior was evaluated by open field test (OFT) and elevated plus maze (EPM) test, while depression-like behavior was evaluated by sucrose preference test (SPT), tail suspension test (TST) and forced swim test (FST). The spatial learning and memory ability were evaluated by Morris water maze (MWM) experiments. The levels of amino acid neurotransmitters were determined by liquid chromatography-mass spectrometry (LC-MS). The histology of the brain was examined by hematoxylin-eosin (HE) staining. It was found that the depression-like behavior, spatial memory ability and histology of the brain did not change obviously after RF exposure. However, the anxiety-like behavior increased in mice, while, the levels of γ-aminobutyric acid (GABA) and aspartic acid (Asp) in cortex and hippocampus significantly decreased after RF exposure. These data suggested that RF exposure under these conditions do not affect the depression-like behavior, spatial memory and brain histology in adolescent male mice, but it may however increase the level of anxiety, and GABA and Asp were probably involved in this effect.

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Section: Discussionmentioning

confidence: 99%

Effects of 1.8 GHz Radiofrequency Fields on the Emotional Behavior and Spatial Memory of Adolescent Mice

Zhang

Guo

et al. 2017

IJERPH

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“…Interestingly, we observed no locomotor changes in efavirenz (5 mg/kg), THC and THC + efavirenz exposed animals in the sub-chronic study. In fact, a recent study 16 also came to the same conclusion concerning acute or sub-chronic efavirenz, despite exploring higher dosages (25 and 50 mg/kg). Moreover, locomotor activity following cannabinoid administration is either unaltered 45 or suppressed at high (20–30 mg/kg) but not low dosages (0.75 mg/kg) 46 of THC 47 , thus emphasizing the variable nature of this parameter.…”

Section: Discussionmentioning

confidence: 70%

“…Although we did not investigate higher aversive doses of efavirenz (e.g. 20 mg/kg), such high doses increase depressive-like behaviour in rats 16 , thus supportive of a dose-dependent balance between its rewarding effects (risk of abuse) vs. neuropsychiatric side-effects such as depression and anhedonia 2 .…”

Section: Discussionmentioning

confidence: 81%

“…Altered redox in turn alters neurotransmitter release 58 and is implicated in mood and psychotic disorders 59 , 60 . Efavirenz treatment is also associated with elevated striatal glutamate levels 16 which may induce oxidative stress. Alternatively, high dosages of efavirenz are associated with elevated plasma levels of 8-hydroxy-efavirenz, a known pro-oxidant thought to underlie the neuropsychiatric effects of efavirenz 2 , 56 , 61 .…”

Section: Discussionmentioning

confidence: 99%

“…Exposure of rats to efavirenz (10 and 30 mg/kg) has been found to significantly decrease exploratory behaviour, although without evidence for addictive-like effects 6 , while another study described anxiogenic and depressogenic effects following acute and sub-chronic doses of efavirenz (25 and 50 mg/kg, respectively) 16 . The authors also found that acute doses of efavirenz (25 mg and 50 mg/kg) increased striatal DA, 5-HT and NA, with sub-chronic exposure having the opposite effect 16 . Thus, dose related neurochemical and psychotropic effects are evident with efavirenz, at least in animals.…”

Section: Introductionmentioning

confidence: 99%

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Efavirenz exposure, alone and in combination with known drugs of abuse, engenders addictive-like bio-behavioural changes in rats

Möller

Fourie

Harvey

2018

Sci Rep

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Efavirenz is abused in a cannabis-containing mixture known as Nyaope. The addictive-like effects of efavirenz (5, 10 and 20 mg/kg) was explored using conditioned place preference (CPP) in rats following sub-acute exposure vs. methamphetamine (MA; 1 mg/kg) and Δ9-tetrahydrocannabinol (THC; 0.75 mg/kg). The most addictive dose of efavirenz was then compared to THC alone and THC plus efavirenz following sub-chronic exposure using multiple behavioural measures, viz. CPP, sucrose preference test (SPT) and locomotor activity. Peripheral superoxide dismutase (SOD), regional brain lipid peroxidation and monoamines were also determined. Sub-acute efavirenz (5 mg/kg) had a significant rewarding effect in the CPP comparable to MA and THC. Sub-chronic efavirenz (5 mg/kg) and THC + efavirenz were equally rewarding using CPP, with increased cortico-striatal dopamine (DA), and increased lipid peroxidation and SOD. Sub-chronic THC did not produce CPP but significantly increased SOD and decreased hippocampal DA. Sub-chronic THC + efavirenz was hedonic in the SPT and superior to THC alone regarding cortico-striatal lipid peroxidation and sucrose preference. THC + efavirenz increased cortico-striatal DA and decreased serotonin (5-HT). Concluding, efavirenz has dose-dependent rewarding effects, increases oxidative stress and alters regional brain monoamines. Efavirenz is hedonic when combined with THC, highlighting its abuse potential when combined with THC.

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Bidirectional Associations among Nicotine and Tobacco Smoke, NeuroHIV, and Antiretroviral Therapy

Ghura

Gross

Jordan‐Sciutto

et al. 2019

J Neuroimmune Pharmacol

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HIV antiretroviral drug Efavirenz induces anxiety-like and depression-like behavior in rats: evaluation of neurotransmitter alterations in the striatum

Cited by 21 publications

References 45 publications

Effects of 1.8 GHz Radiofrequency Fields on the Emotional Behavior and Spatial Memory of Adolescent Mice

Effects of 1.8 GHz Radiofrequency Fields on the Emotional Behavior and Spatial Memory of Adolescent Mice

Efavirenz exposure, alone and in combination with known drugs of abuse, engenders addictive-like bio-behavioural changes in rats

Bidirectional Associations among Nicotine and Tobacco Smoke, NeuroHIV, and Antiretroviral Therapy

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