5-HT2C receptor activation prevents stress-induced enhancement of brain 5-HT turnover and extracellular levels in the mouse brain: modulation by chronic paroxetine treatment.
Stress is known to activate the central 5-hydroxytryptamine (5-HT) system, and this is probably part of a coping response involving several 5-HT receptors. Although 5-HT(2C) receptors are well known to be implicated in anxiety, their participation in stress-induced changes had not been investigated in parallel at both behavioral and neurochemical levels. We show here that the preferential 5-HT(2C) receptor agonist, m-chlorophenylpiperazine, as well as restraint stress increased anxiety in the mouse social interaction test. The selective 5-HT(2C) receptor antagonist, SB 242,084, prevented both of these anxiogenic effects. Restraint stress increased 5-HT turnover in various brain areas, and this effect was prevented by the 5-HT(2B/2C) receptor agonist RO 60-0175 (1 mg/kg), but not the preferential 5-HT(2A) agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (1 mg/kg), and in contrast potentiated by SB 242,084 (1 mg/kg), which also blocked the effect of RO 60-0175. Using microdialysis, RO 60-0175 was shown to inhibit cortical 5-HT overflow in stressed mice when 5-HT reuptake was blocked locally. Chronic paroxetine prevented both the anxiogenic effect of m-chlorophenylpiperazine and the inhibitory effect of RO 60-0175 on locomotion and stress-induced increase in 5-HT turnover. The anxiolytic action of chronic paroxetine might be associated with an enhancement of 5-HT neurotransmission caused by a decreased 5-HT(2C) receptor-mediated inhibition of stress-induced increase in 5-HT release.
Mongeau
Raymond
R
INSERM UMR S894, Paris, France. raymond.mongeau@chups.jussieu.fr
Martin
Cédric B P
CB
Chevarin
Caroline
C
Maldonado
Rafael
R
Hamon
Michel
M
Robledo
Patricia
P
Lanfumey
Laurence
L
D000662:Amphetamines / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology*; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D005021:Ethylamines / Q000494:pharmacology; D045604:Extracellular Fluid / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D007398:Interpersonal Relations; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009043:Motor Activity / Q000187:drug effects; D017374:Paroxetine / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D044405:Receptor, Serotonin, 5-HT2C / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D013315:Stress, Psychological / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D000662:Amphetamines; D018687:Antidepressive Agents, Second-Generation; D005021:Ethylamines; D007211:Indoles; D010879:Piperazines; D044405:Receptor, Serotonin, 5-HT2C; C103848:Ro 60-0175; D017366:Serotonin Receptor Agonists; D012701:Serotonin; D017374:Paroxetine; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; C015068:1-(3-chlorophenyl)piperazine