Long-term administration of m-chlorophenylpiperazine (mCPP) to rats induces changes in serotonin receptor binding, dopamine levels and locomotor activity without altering prolactin and corticosterone secretion.
Meta-chlorophenylpiperazine (mCPP) is a serotonin (5-HT) agonist with antidepressant actions. In order to investigate the effects of chronic mCPP treatment the drug was administered to rats for 15 days (5 mg/kg twice daily). Controls were administered saline. Long-term mCPP treatment led to a 36% increase in [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) binding to 5-HT1a receptors in hippocampus and a 74% decrease in [3H]ketanserin binding to 5-HT2 receptors in cortex, while (-)[125I]iodocyanopindolol ([125I]CYP) binding to 5-HT1b receptors in hypothalamus and striatum was unchanged. In hypothalamus, chronic mCPP treatment decreased the levels of dopamine (DA) but not 5-HT. The usual suppression of locomotor activity induced by acute mCPP administration was less after long-term mCPP treatment. Brain and plasma levels of mCPP following an acute dose were not different between controls and rats previously administered mCPP, suggesting that altered rate of metabolism of the drug did not explain the tolerance to the mCPP-induced decrease in locomotor activity. mCPP-induced prolactin (PRL) and corticosterone release were not changed by previous long-term mCPP administration. Thus, chronic mCPP administration to rats induced alterations in density of 5-HT receptor subtypes, hypothalamic levels of DA and locomotor behavior.
Neuroendocrinology/Immunology Laboratory, National Institute on Drug Abuse, Baltimore, MD 21224.
J
J
Ulrichsen
J S
JS
Partilla
E M
EM
Dax
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D018377:Neurotransmitter Agents / Q000378:metabolism; D010879:Piperazines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects*
D018377:Neurotransmitter Agents; D010879:Piperazines; D011985:Receptors, Serotonin; D011388:Prolactin; C015068:1-(3-chlorophenyl)piperazine; D004298:Dopamine; D003345:Corticosterone