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.

Fatty acids differentially affect serotonin receptor and transporter binding in the rat brain.

The aim of this study was to examine the influence of different fat diets on serotonin receptor and transporter binding. Male Sprague-Dawley rats were fed a diet of either high saturated fat, omega-6 polyunsaturated fatty acid, omega-3 polyunsaturated fatty acid or low fat (control) for eight weeks. Using Beta-Imager quantification techniques, [(3)H]ketanserin, [(3)H]mesulergine and [(3)H]paroxetine binding to serotonin (5-HT)(2A), 5-HT(2C) receptors and 5-HT transporters (5-HTT) was measured throughout the brain in all four groups. All three high fatty acid diets influenced serotonin receptor binding, however the most pronounced effects were that compared with the low fat control group, i) 5-HT(2A) receptor binding was increased in the caudate putamen, but reduced in the mammillary nucleus in high saturated fat and high omega-6 polyunsaturated fatty acid diet groups; ii) 5-HT(2C) receptor binding was reduced in the mamillary nucleus of saturated fat group and reduced in prefrontal cortex of the omega-6 polyunsaturated fatty acid and omega-3 polyunsaturated fatty acid groups; and iii) 5-HTT binding was reduced in the hippocampus in the omega-6 polyunsaturated fatty acid group. Overall, the omega-6 polyunsaturated fatty acid diet exerted the most influence on serotonin receptor and transporter binding. These results may be of importance in relation to neuropsychiatric diseases such as schizophrenia, where associations between altered fatty acid levels and the serotonergic system have been made.