Abstract
Administration of lithium chloride (10 mmol/kg on day 1 and 3 mmol/kg twice daily on subsequent days, SC) for 3–14 days enhances the components of the serotonin syndrome produced by 8-hydroxy-2-(di-propylamino)tetralin (8-OH-DPAT) in the rat. The hypothermic response produced simultaneously was unaltered. Following lithium administration for 3 days the motor response to 5-methoxy,N,N-dimethyltryptamine was also facilitated. These data suggest that lithium administration enhances post-synaptic 5-HT receptor-mediated behavioural responses.
(−)-Propranolol (20 mg/kg, IP) but not (+)-propranolol (20 mg/kg IP) fully antagonised the facilitated response to 8-OH-DPAT seen following lithium administration; ritanserin (200 μg/kg, IP) was without effect. These findings favour a mechanism for the action of lithium involving the 5-HT1A receptor.
Depletion of 5-hydroxytryptamine (5-HT) with parachlorophenylalanine (PCPA, 300 mg/kg, IP on day 1 and 2 of lithium administration) did not prevent the facilitation by lithium of the response to 8-OH-DPAT. These data strengthen the suggestion that lithium has its effect on 5-HT1A-mediated motor function by a post-synaptic action.
By contrast, motor responses to the putative 5-HT1B receptor agonist 5-methoxy-3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole (RU 24969) were unaltered by repeated lithium administration.
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Goodwin, G.M., De Souza, R.J., Wood, A.J. et al. The enhancement by lithium of the 5-HT1A mediated serotonin syndrome produced by 8-OH-DPAT in the rat: evidence for a post-synaptic mechanism. Psychopharmacology 90, 488–493 (1986). https://doi.org/10.1007/BF00174066
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DOI: https://doi.org/10.1007/BF00174066