Intraperitoneal administration of 1-(2,5-dimethoxy-4-iodophenyl)-2- aminopropane (DOI) produced significant decreases in the first-hour food intake on day 1 and on day 2 relative to saline-treated animals. Complete tolerance developed to DOI-induced hypophagia by day 3. However, there was no cross-tolerance to m-chlorophenylpiperazine (m- CPP)-induced hypophagia. Similarly, complete tolerance developed to m- CPP-induced hypophagia by day 3, but again there was no cross-tolerance to DOI-induced hypophagia. These findings suggest that DOI and m-CPP- induced hypophagia are mediated by different mechanisms, most likely by selective stimulation of 5-HT2A receptors by DOI and 5-HT2C receptors by m-CPP. In another study, the phenylisopropylamine hallucinogen 1- (2,5- dimethoxy-4-methylphenyl)-2-aminopropane (DOM) produced dose-related increases in plasma concentrations of prolactin, adrenocorticotropic hormone (ACTH) and corticosterone but not growth hormone in rats. By using various 5-HT receptor subtype-selective antagonists, we have demonstrated involvement of 5-HT2A/5-HT2C and 5-HT3 receptors in mediating DOM-induced increases in plasma prolactin, whereas DOM-induced increases in ACTH appear to be mediated by stimulation of 5-HT2A receptors. DOM-induced corticosterone secretion appears to be mediated by stimulation of 5-HT2A and/or 5-HT2C receptors. In a separate series of experiments, the temperature increases induced by either DOI or m-CPP were found to be significantly less in Fawn-Hooded rats (FH) (a rat strain suggested to represent a genetic model of depression and other neuropsychiatric disorders) relative to Wistar rats. Long-term (21 days) treatment with the tricyclic antidepressants, imipramine or clomipramine, attenuated DOI-induced hyperthermia, while m-CPP-induced hyperthermia was accentuated in FH rats. On the other hand, long-term (21 days) treatment with the monoamine oxidase type-A inhibiting antidepressant, clorgyline, did not modify m-CPP-induced hyperthermia, but significantly attenuated DOI-induced hyperthermia in FH rats. These findings demonstrate that long-term antidepressant treatments alter 5-HT2C and 5-HT2A receptor- mediated hyperthermia in a genetic animal model of depression.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Intramural Research (Z01)
Project #
1Z01MH000332-17
Application #
5203649
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
17
Fiscal Year
1995
Total Cost
Indirect Cost
Name
U.S. National Institute of Mental Health
Department
Type
DUNS #
City
State
Country
United States
Zip Code
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