Brain Angiotensin II (Ang II) participates in the regulation of fluid and electrolyte homeostasis, hormone secretion, central and peripheral sympathetic activity. Through stimulation of the physiologically active AT1 receptors, Ang II controls the response of the hypothalamic-pituitary-adrenal axis and the brain and peripheral sympathetic activity during stress. The stress response activate the same neuronal pathways that psychostimulant drugs like cocaine and amphetamine. Several studies have been confirmed that stress increase the individual vulnerability to drug abuse autoadministration. Our purpose was to study the possible role of the brain Ang II in the locomotor sensitization induced by amphetamine. Male rats weighing 250-300 g were treated during 5 days with 3mg/kg candesartan cilexetil (AT1 antagonist) orally and 24h later received one injection of 5 mg/kg amphetamine (Amph). The animals were tested one or three weeks later using a challenge of 0.5 mg/kg of Amph and the locomotor activity was registered during 2 hours. We found that the locomotor sensitization induced by Amph was higher after 3 weeks of 5 mg/kg Amph injection, this effect was attenuated by the blockade of the at1 receptor. The antagonist treatment induced a slightly increase in the locomotor activity when tested 3 weeks later. No effect of the antagonist was found after one week injection. We also found that 5 days of the AT1 receptor antagonist decreased the noradrenergic activity in the locus coeruleus. These results suggest a possible role of brain Ang II in the sensitization induced by Amph.
