Schizophrenia-like endurable behavioral and neuroadaptive changes induced by ketamine administration involve Angiotensin II AT receptor.

Schizophrenia is a chronic disease affecting 1% worldwide population, of which 30% are refractory to the available treatments: thus, searching for new pharmacological targets is imperative. The acute and repeated ketamine administration are validated preclinical models that recreate the behavioral and neurochemical features of this pathology, including the parvalbumin-expressing interneurons dysfunction. Angiotensin II, through AT receptors (AT-R), modulates the dopaminergic and GABAergic neurotransmission.

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.

Amphetamine-induced neuroadaptations involve vascular damage, neuroinflammation, a hypo-functioning prefrontal cortex (PFC), and cognitive alterations. Brain angiotensin II, through angiotensin type 1 receptor (AT -R), mediates oxidative/inflammatory responses, promoting endothelial dysfunction, neuronal oxidative damage and glial reactivity. The present work aims to unmask the role of AT -R in the development of amphetamine-induced changes over glial and vascular components within PFC and hippocampus.

Brain Angiotensin II Involvement in Chronic Mental Disorders.

Background: The functioning of the central nervous system is complex and it implies tight and coordinated interactions among multiple components. Neurotransmitters systems imbalance is a hallmark in the central nervous system (CNS) disorders. These pathologies profoundly impact the social, cultural, and economic perspective worldwide.

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

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.

Brain Angiotensin II AT1 receptors are involved in the acute and long-term amphetamine-induced neurocognitive alterations.

Rationale: Angiotensin II, by activation of its brain AT1-receptors, plays an active role as neuromodulator in dopaminergic transmission. These receptors participate in the development of amphetamine-induced behavioral and dopamine release sensitization. Dopamine is involved in cognitive processes and provides connectivity between brain areas related to these processes.

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

A single or repeated exposure to psychostimulants induces long-lasting neuroadaptative changes. Different neurotransmitter systems are involved in these responses including the neuropeptide angiotensin II. Our study tested the hypothesis that the neuroadaptative changes induced by amphetamine produce alterations in brain RAS components that are involved in the expression of the locomotor sensitization to the psychostimulant drug.

Angiotensin II AT₁ receptors are involved in neuronal activation induced by amphetamine in a two-injection protocol.

It was already found that Ang II AT₁ receptors are involved in the neuroadaptative changes induced by a single exposure to amphetamine, and such changes are related to the development of behavioral and neurochemical sensitization. The induction of the immediately early gene c-fos has been used to define brain activated areas by amphetamine. Our aim was to evaluate the participation of AT₁ receptors in the neuronal activation induced by amphetamine sensitization.