Antagonizing effect of lithium on the development of dopamine supersensitivity in the tuberoinfundibular system

We investigated whether receptor supersensitivity occurs in the tuberoinfundibular dopaminergic system, as reported in the nigrostriatal and mesolimbic areas. Animals received either haloperidol or saline for 2 weeks. Five days after the last injection of haloperidol, animals pretreated with haloperidol showed a significantly longer lasting inhibition of prolactin (PRL) secretion by apomorphine, compared with the controls. This dopamine receptor supersensitivity was also observed on the 12th, but not the 33rd day after the cessation of haloperidol administration. The effect of lithium on this dopamine supersensitivity in PRL release was investigated. All rats were treated with haloperidol and fed either a diet containing lithium carbonate or a diet without lithium for 2 weeks. Lithium administration with haloperidol resulted in the inhibition of PRL-lowering action of apomorphine at 5 days of withdrawal from haloperidol, indicating that the supersensitivity of dopamine receptors of dopamine receptors on pituitary lactotrophs were decreased by lithium. This action of lithium may be related to the prophylactic effect of the drug on the manic-depressive disease.