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.
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 micrograms/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.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002230:Carbidopa / Q000494:pharmacology; D004357:Drug Synergism; D010134:Fenclonine / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008732:Methoxydimethyltryptamines / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects*; D009281:Naphthalenes / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000502:physiology*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D007211:Indoles; D008732:Methoxydimethyltryptamines; D009281:Naphthalenes; D011985:Receptors, Serotonin; D013764:Tetrahydronaphthalenes; C025145:5-methoxy 3-(1,2,3,6-tetrahydro-4-pyridinyl)1H indole; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D008094:Lithium; D011433:Propranolol; D006916:5-Hydroxytryptophan; D002230:Carbidopa; D010134:Fenclonine