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 receptor antagonist, MK-801, significantly disrupted PPI. There was, however, no difference in these effects between the genotypes. These data suggest that genetically induced changes in the activity of the angiotensin system do not alter regulation of PPI in mice. Our previous results on the effects of reduced ACE activity could be explained by mechanisms other than angiotensin, such as effects on enkephalin or bradykinin metabolism.
Behavioural Neuroscience Laboratory, Mental Health Research Institute of Victoria, 155 Oak Street, Parkville (Melbourne), Victoria 3052, Australia.
Sally
S
Martin
M Andrea
MA
Markus
Brian J
BJ
Morris
Robin L
RL
Davisson
Andrew J
AJ
Lawrence
Maarten
M
van den Buuse
D000661:Amphetamine / Q000494:pharmacology; D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001058:Apomorphine / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects* / Q000502:physiology*; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D018491:Dopamine Agonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology; D004742:Enhancer Elements, Genetic / Q000235:genetics / Q000502:physiology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D010751:Phosphopyruvate Hydratase / Q000235:genetics / Q000502:physiology; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects*; D012083:Renin / Q000235:genetics / Q000502:physiology
D000809:Angiotensins; D018491:Dopamine Agonists; D018765:Dopamine Uptake Inhibitors; D018691:Excitatory Amino Acid Antagonists; D044140:Receptor, Angiotensin, Type 1; D016291:Dizocilpine Maleate; D000661:Amphetamine; D012083:Renin; D010751:Phosphopyruvate Hydratase; D001058:Apomorphine; D004298:Dopamine