Hypersensitivity to meta-chlorophenylpiperazine (mCPP) in migraine and drug withdrawal

Administration of a bolus dose of mCPP, a 5-HT2C receptor agonist, to rats provokes endocrine and behavioural effects that are reminiscent of some of the symptoms of human depression. Rats exposed to chronic mild stress (which is also a key factor in the precipitation of human depression) were hypersensitive to mCPP, whilst chronic treatment with antidepressant serotonin re-uptake inhibitors suppressed the responsiveness to mCPP. Similarities also exist with respect to withdrawal reactions following chronic alcohol or benzodiazepine abuse. In humans, a bolus dose of mCPP can cause alcohol craving (in abstinent alcoholics) and migraine (in susceptible persons), suggesting that there is a 5-HT2C receptor hyperresponsiveness in these conditions also. It is hypothesized that chronic treatment with SSRI's can prevent migraine attacks and drug craving.