Long-term neuroleptic treatments counteract dopamine D sub(2) agonist inhibition of adenylate cyclase but do not affect pertussis toxin ADP-ribosylation in the rat brain

• Published in: Neurochemistry international 1996-02, Vol.28 (2), p.161-168
• Main Authors: Okada, F, Ito, A, Horikawa, T, Tokumitsu, Y, Nomura, Y
• Format: Article
• Language: English
• Subjects: Bordetella pertussis
• ISSN: 0197-0186

We have investigated the response of adenylate cyclase to GTP and to dopamine (DA) in striatal membranes of rats treated for 3 weeks with chlorpromazine or haloperidol, and further measured the level of Gi (an inhibitory GTP-binding protein) or Go (a similar GTP-binding protein of unknown function) in 3 areas (cerebral cortex, striatum and hippocampus) utilizing pertussis toxin-catalyzed ADP ribosylation. In saline-treated control membranes, GTP exerted a biphasic effect on basal and DA-stimulated enzyme activity--peak levels of stimulation by DA plus GTP were observed at 1 mu M GTP. Conversely, dopaminergic inhibitory effects at 10-100 mu M GTP were completely attenuated in chlorpromazine or haloperidol-treated membranes. D sub(2) inhibition of adenylate cyclase by the selective D sub(2) agonist PPHT was also attenuated due to these neuroleptic treatments, while an increase in D sub(2) receptor binding was observed. The pertussis toxin ADP-ribosylation of G-proteins (Gi/Go) did not differ significantly in any area. This indicates that long-term neuroleptic treatments increased D sub(2) receptor binding, but attenuated D sub(2) inhibition of adenylate cyclase, and exercised no influence on pertussis toxin ADP-ribosylation.