The effects of antipsychotic drugs administration on 5-HT1A receptor expression in the limbic system of the rat brain.
Increasing evidence suggests that 5-HT1A receptors are involved in the pathophysiology and treatment of schizophrenia. This paper investigated 5-HT1A receptor mRNA expression and binding density in female rats treated with aripiprazole (2.25 mg/kg/day), olanzapine (1.5 mg/kg/day), haloperidol (0.3 mg/kg/day) or vehicle (control) orally three times/day for 1 or 12 weeks. Animals were sacrificed 48 h after the last administration. Aripiprazole significantly increased 5-HT1A receptor binding density by 33% in the CA1 region of the hippocampus and by 21% in the medial posterodorsal nuclei of posterior amygdala (MeP) compared to the control group after 1 week of treatment. Olanzapine significantly decreased 5-HT1A receptor binding density by 17-22% in Layers I-IV of the cingulate cortex after 1 week of treatment. Neither of these antipsychotic drugs affected 5-HT1A receptor binding density after 12 weeks drug treatment. As expected, haloperidol treatment did not have any significant effect on 5-HT1A binding density after 1 or 12 weeks of treatment. 5-HT1A receptor mRNA expression was not altered by antipsychotic treatment in any brain region. The results indicate that aripiprazole and olanzapine have differential effects on 5-HT1A receptor expression, which may contribute to their distinct profiles in improving negative symptoms and cognitive deficits in schizophrenia. Aripiprazole and olanzapine may produce adaptation and desensitization of 5-HT1A receptor expression after long term treatment.
Han
M
M
Centre for Translational Neuroscience, School of Health Sciences, University of Wollongong, Northfields Avenue, Wollongong, NSW 2522, Australia.
Huang
X F
XF
du Bois
T M
TM
Deng
C
C
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D000068180:Aripiprazole; D001569:Benzodiazepines / Q000494:pharmacology; D001665:Binding Sites; D005260:Female; D006220:Haloperidol / Q000494:pharmacology; D008032:Limbic System / Q000033:anatomy & histology / Q000187:drug effects* / Q000378:metabolism; D000077152:Olanzapine; D010879:Piperazines / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D044263:Receptors, Serotonin, 5-HT1 / Q000096:biosynthesis* / Q000235:genetics
D014150:Antipsychotic Agents; D010879:Piperazines; D015363:Quinolones; D012333:RNA, Messenger; D044263:Receptors, Serotonin, 5-HT1; D001569:Benzodiazepines; D000068180:Aripiprazole; D006220:Haloperidol; D000077152:Olanzapine