Involvement of the brain renin–angiotensin system (RAS) in the neuroadaptive responses induced by amphetamine in a two-injection protocol

Paz, Maria Constanza; Marchese, Natalia Andrea; Stroppa, María Mercedes; Burgos, Nelia Marta Gerez de; Imboden, Hans; Baiardi, Gustavo; Cancela, Liliana Marina; Bregonzio, Claudia

doi:10.1016/j.bbr.2014.07.021

Cited by 21 publications

(15 citation statements)

References 54 publications

(75 reference statements)

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“…It is recognized that exposure to psychostimulants allows the identification of region‐specific alterations (Ellison & Switzer, ). These alterations also include the angiotensinergic system since Amph or methamphetamine induces an increase in AT 1 ‐R expression and activity, in specific brain areas (Jiang et al, ; Paz et al, ). Interestingly, Amph affected the analyzed glial and vascular components selectively in the PFC, whereas none of the studied alterations were observed at HPC (Figure ).…”

Section: Discussionmentioning

confidence: 99%

“…Our previous reports support the AT 1 ‐R involvement in the development of Amph‐induced neuroadaptations at neurochemical, structural, and behavioral levels (Paz, Assis, Cabrera, Cancela, & Bregonzio, ; Paz, Marchese, Cancela, & Bregonzio, ; Occhieppo et al, ). Moreover, a long‐lasting overexpression of functional AT 1 ‐R was observed in DA‐innervated areas after Amph exposure (Paz et al, ), whereas altered AT 1 ‐R functionality was described regarding classical AngII‐elicited actions (Casarsa et al, ). In the present study, we aimed to characterize the pattern of Amph‐induced deleterious effects, over microglia and astrocyte activation along with vascular network organization in PFC and HPC, and how the AT 1 ‐R modulates those effects.…”

Section: Introductionmentioning

confidence: 99%

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Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Marchese

Occhieppo

Basmadjian

et al. 2019

Eur J of Neuroscience

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Amphetamine‐induced neuroadaptations involve vascular damage, neuroinflammation, a hypo‐functioning prefrontal cortex (PFC), and cognitive alterations. Brain angiotensin II, through angiotensin type 1 receptor (AT1‐R), mediates oxidative/inflammatory responses, promoting endothelial dysfunction, neuronal oxidative damage and glial reactivity. The present work aims to unmask the role of AT1‐R in the development of amphetamine‐induced changes over glial and vascular components within PFC and hippocampus. Attention deficit was evaluated as a behavioral neuroadaptation induced by amphetamine. Brain microvessels were isolated to further evaluate vascular alterations after amphetamine exposure. Male Wistar rats were administered with AT1‐R antagonist, candesartan, followed by repeated amphetamine. After one week drug‐off period, animals received a saline or amphetamine challenge and were evaluated in behavioral tests. Afterward, their brains were processed for cresyl violet staining, CD11b (microglia marker), GFAP (astrocyte marker) or von Willebrand factor (vascular marker) immunohistochemistry, and oxidative/cellular stress determinations in brain microvessels. Statistical analysis was performed by using factorial ANOVA followed by Bonferroni or Tukey tests. Repeated amphetamine administration increased astroglial and microglial markers immunoreactivity, increased apoptotic cells, and promoted vascular network rearrangement at the PFC concomitantly with an attention deficit. Although the amphetamine challenge improved the attentional performance, it triggers detrimental effects probably because of the exacerbated malondialdehyde levels and increased heat shock protein 70 expression in microvessels. All observed amphetamine‐induced alterations were prevented by the AT1‐R blockade. Our results support the AT1‐R involvement in the development of oxidative/inflammatory conditions triggered by amphetamine exposure, affecting cortical areas and increasing vascular susceptibility to future challenges.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Marchese

Occhieppo

Basmadjian

et al. 2019

Eur J of Neuroscience

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“…Our initial studies were focused on AT 1 ‐R involvement in the development of Amph‐induced sensitisation, which implies neuroadaptative responses. In this sense, AT 1 ‐R antagonism blunted the increased dopaminergic neurotransmission in striatal areas and the augmented locomotor activity in response to a challenge (Paz et al ., , , ). Furthermore, our recently published data extended AT 1 ‐R role in Amph‐induced neuroadaptations in nonstriatal areas and their related outcomes (Marchese et al ., ).…”

Section: Introductionmentioning

confidence: 99%

Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT₁ receptor activation

Occhieppo

Marchese

Rodriguez

et al. 2017

Eur J of Neuroscience

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The use of psychostimulants, such as amphetamine (Amph), is associated with inflammatory processes, involving glia and vasculature alterations. Brain Angiotensin II (Ang II), through AT -receptors (AT -R), modulates neurotransmission and plays a crucial role in inflammatory responses in brain vasculature and glia. Our aim for the present work was to evaluate the role of AT -R in long-term alterations induced by repeated exposure to Amph. Astrocyte reactivity, neuronal survival and brain microvascular network were analysed at the somatosensory cortex. Thermal nociception was evaluated as a physiological outcome of this brain area. Male Wistar rats (250-320 g) were administered with AT -R antagonist Candesartan/vehicle (3 mg/kg p.o., days 1-5) and Amph/saline (2.5 mg/kg i.p., days 6-10). The four experimental groups were: Veh-Sal, CV-Sal, Veh-Amph, CV-Amph. On day 17, the animals were sacrificed and their brains were processed for Nissl staining and immunohistochemistry against glial fibrillary acidic protein (GFAP) and von Willebrand factor. In another group of animals, thermal nociception was evaluated using hot plate test, in the four experimental groups, on day 17. Data were analysed with two-way anova followed by Bonferroni test. Our results indicate that Amph exposure induces an increase in: neuronal apoptosis, astrocyte reactivity and microvascular network, evaluated as an augmented occupied area by vessels, branching points and their tortuosity. Moreover, Amph exposure decreased the thermal nociception threshold. Pretreatment with the AT -R blocker prevented the described alterations induced by this psychostimulant. The decreased thermal nociception and the structural changes in somatosensory cortex could be considered as extended neuroadaptative responses to Amph, involving AT -R activation.

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“…In fact, the interaction between the dopaminergic system and the RAS has long been discovered by microdialysis studies in brain, which showed that acute Ang II perfusion induces dopamine release, which is blocked by AT 1 -R antagonists [16]. Although the involvement of AT 1 -R in neuronal activation and AMPH-induced hyperlocomotion has been known [22][23][24], the role of AT 1 -R as well as ACE in METH effect is largely unknown. Pretreatment with AMPH in rats showed an elevated AT 1 -R expression both in mRNA and protein levels in the striatum and NAc [24].…”

Section: Discussionmentioning

confidence: 99%

“…Studies suggest that interaction between AT 1 -R and amphetamine (AMPH) participates in the neuroadaptative and long-term changes in AT 1 -R density as well as angiotensinogen expression [22,23]. Increased locomotor activity induced by AMPH challenge is inhibited by AT 1 -R antagonist losartan administration in the caudate putamen of rats [24]. AT 1 -R is also involved in learning and memory alterations induced by amphetamine in rats [25].…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

Brain Renin–Angiotensin System Blockade Attenuates Methamphetamine-Induced Hyperlocomotion and Neurotoxicity

Jiang

Zhu

et al. 2018

Neurotherapeutics

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Methamphetamine (METH) abuse has become a major public health concern worldwide without approved pharmacotherapies. The brain renin-angiotensin system (RAS) is involved in the regulation of neuronal function as well as neurological disorders. Angiotensin II (Ang II), which interacts with Ang II type 1 receptor (AT-R) in the brain, plays an important role as a neuromodulator in dopaminergic transmission. However, the role of brain RAS in METH-induced behavior is largely unknown. Here, we revealed that repeated METH administration significantly upregulated the expression of AT-R in the striatum of mice, but downregulated dopamine D3 receptor (D3R) expression. A specific AT-R blocker telmisartan, which can penetrate the brain-blood barrier (BBB), or genetic deletion of AT-R was sufficient to attenuate METH-triggered hyperlocomotion in mice. However, intraperitoneal injection of AT-R blocker losartan, which cannot penetrate BBB, failed to attenuate METH-induced behavior. Moreover, intra-striatum re-expression of AT with lentiviral virus expressing AT reversed the weakened locomotor activity of AT mice treated with METH. Losartan alleviated METH-induced cytotoxicity in SH-SY5Y cells in vitro, which was accompanied by upregulated expressions of D3R and dopamine transporter. In addition, intraperitoneal injection of perindopril, which is a specific ACE inhibitor and can penetrate BBB, significantly attenuated METH-induced hyperlocomotor activity. Collectively, our results show that blockade of brain RAS attenuates METH-induced hyperlocomotion and neurotoxicity possibly through modulation of D3R expression. Our findings reveal a novel role of Ang II-AT-R in METH-induced hyperlocomotion.

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Involvement of the brain renin–angiotensin system (RAS) in the neuroadaptive responses induced by amphetamine in a two-injection protocol

Cited by 21 publications

References 54 publications

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT₁ receptor activation

Brain Renin–Angiotensin System Blockade Attenuates Methamphetamine-Induced Hyperlocomotion and Neurotoxicity

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Involvement of the brain renin–angiotensin system (RAS) in the neuroadaptive responses induced by amphetamine in a two-injection protocol

Cited by 21 publications

References 54 publications

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Angiotensin II modulates amphetamine‐induced glial and brain vascular responses, and attention deficit via angiotensin type 1 receptor: Evidence from brain regional sensitivity to amphetamine

Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT1 receptor activation

Brain Renin–Angiotensin System Blockade Attenuates Methamphetamine-Induced Hyperlocomotion and Neurotoxicity

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Neurovascular unit alteration in somatosensory cortex and enhancement of thermal nociception induced by amphetamine involves central AT₁ receptor activation