Does angiotensin interact with dopaminergic mechanisms in the brain to modulate prepulse inhibition in mice?
Changes in the levels of angiotensin-converting enzyme (ACE) have been found in brains of schizophrenia patients, suggesting a possible involvement of angiotensin in the illness. Prepulse inhibition (PPI) is a measure of sensorimotor gating and is disrupted in patients with schizophrenia. In a previous study, a reduction of ACE activity, either in ACE knockout mice or after ACE inhibitor treatment, markedly inhibited the disruption of PPI caused by the dopamine receptor agonist, apomorphine. ACE is not specific for the angiotensin system and, therefore, in the present study we assessed pharmacological regulation of PPI in two other, more specific genetic mouse models of altered angiotensin activity. We used renin-enhancer knockout (REKO) mice, which display reduced renin activity, and neuron-specific enolase (NSE)-AT1A mice, which selectively over-express angiotensin AT1A receptors in the brain. Treatment of these mice with apomorphine, the dopamine releaser, amphetamine or the NMDA re
