Long-term lithium treatment causes serotonin receptor down-regulation

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Long-term lithium treatment causes serotonin receptor down-regulation

via serotonergic presynapses in rat brain.

Hotta I, Yamawaki S, Segawa T.

The effects of lithium treatment on serotonin (5-HT) receptors in rat

frontal cortex and hippocampus were investigated. Long-term lithium

treatment strongly blocked 5-hydroxytryptophan-induced head twitches,

while acute lithium administration by itself induced head twitches in

rats, and ketanserin blocked this acute lithium action. Long-term

administration of lithium decreased the number of not only 5-HT2

receptors in the frontal cortex but also 5-HT1 and 5-HT2 receptors in

the hippocampus in rats. Decreases in 3H-5-HT binding to hippocampal

5-HT1 receptors and 3H-spiperone binding to frontal cortical 5-HT2

receptors, caused by chronic lithium treatment, were abolished by co-

administration of p-chlorophenylalanine, and were enhanced by co-

administration with methiothepin. The turnover of 5-HT in either

frontal cortex or hippocampus was facilitated by lithium, and co-

administered methiothepin enhanced this facilitation. These results

suggest that long-term lithium treatment causes the down-regulation

of postsynaptic 5-HT1 and 5-HT2 receptors, in part probably through

its action on presynaptic nerve terminals.

Publication Types:

In Vitro

Research Support, Non-U.S. Gov't

PMID: 3494960 [PubMed - indexed for MEDLINE]