Long-term lithium treatment causes serotonin receptor down-regulation via serotonergic presynapses in rat brain.
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.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000502:physiology*; D005625:Frontal Lobe / Q000378:metabolism; D006257:Head; D006624:Hippocampus / Q000378:metabolism; D066298:In Vitro Techniques; D007650:Ketanserin / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008719:Methiothepin / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000502:physiology*; D013134:Spiperone / Q000378:metabolism; D013997:Time Factors
D011985:Receptors, Serotonin; D012701:Serotonin; D013134:Spiperone; D008719:Methiothepin; D007650:Ketanserin; D008094:Lithium; D006916:5-Hydroxytryptophan