Effects of haloperidol, clozapine and citalopram on messenger RNA levels of chromogranins A and B and secretogranin II in various regions of rat brain.
We have measured the messenger RNA levels of chromogranins A and B and secretogranin II in various brain regions of rats subchronically treated with various antipsychotic drugs. Since, as shown previously, the messenger RNA levels of these peptides are increased when neurons are stimulated, we hoped to identify by this approach those nuclei which are subchronically influenced by these drugs. The drugs chosen were the neuroleptic halperidol, a blocker of dopamine receptors, the atypical antipsychotic clozapine, which in addition to blocking dopamine receptors also blocks those for serotonin, and citalopram, a specific serotonin reuptake inhibitor. In agreement with previous data on neuropeptide messenger RNAs, we found in the dorsolateral striatum an increase of the secretogranin II messenger RNA levels after haloperidol and a much smaller one after clozapine. In the nucleus accumbens and in the bed nucleus of the stria terminalis, both compounds had a comparable positive effect. These differential effects can be attributed to a different action of these drugs on dopamine receptor subtypes. In the zona incerta, clozapine decreased the secretogranin II and chromogranin A message, whereas in the dorsal raphe it led to an increase. On the other hand, citalopram induced exactly the opposite effects in these two brain regions. This phenomenon can be explained by the differential interaction of these drugs with serotonergic mechanisms. Additional, relatively small changes of the mRNAs were seen in several other brain regions. These results establish that changes in the mRNA levels of the chromogranins are good indicators for the effect of drugs on certain brain nuclei. The concomitant action of haloperidol and clozapine on the limbic regions, i.e. the nucleus accumbens and the bed nucleus of the stria terminalis, points to these brain regions for the antipsychotic action of these two neuroleptics.
Kroesen
S
S
Department of Pharmacology, University of Innsbruck, Austria.
Marksteiner
J
J
Mahata
S K
SK
Mahata
M
M
Fischer-Colbrie
R
R
Saria
A
A
Kapeller
I
I
Winkler
H
H
D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology; D014150:Antipsychotic Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism*; D002864:Chromogranins / Q000235:genetics*; D015283:Citalopram / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D006220:Haloperidol / Q000494:pharmacology*; D008297:Male; D011506:Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution
D000928:Antidepressive Agents; D014150:Antipsychotic Agents; D002864:Chromogranins; D011506:Proteins; D012333:RNA, Messenger; D015283:Citalopram; D003024:Clozapine; D006220:Haloperidol