Effects of chlorisondamine and restraint on cortical [3H]ketanserin binding, 5-HT2A receptor-mediated head shakes, and behaviours in models of anxiety.
A recent study has indicated that ganglionic transmission mediates acute restraint-elicited increases in brain tryptophan (5-HT precursor) levels, 5-HT synthesis and (possibly) release. Because restraint-induced release of 5-HT has been shown to be associated with a paradoxical increase in cortical 5-HT2A receptor binding, we have examined the influence of 5-HT synthesis/release upon cortical 5-HT2A receptor binding and 5-HT2A receptor-mediated head shakes in 3-hr restrained rats pretreated with the ganglionic blocker chlorisondamine. In keeping with past reports regarding the effects of restraint and ganglionic blockade upon anxiety, we have also measured the behavioural effects of restraint and/or chlorisondamine in two animal models of anxiety, the elevated plus-maze and the social interaction test. Chlorisondamine pretreatment (2.5 mg/kg, 20 min beforehand) prevented restraint-elicited defaecation and body weight decreases. Although stress amplified the head shake response to the injection of the 5-HT2A/5-HT2C receptor agonist 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane (DOI, 1 or 2 mg/kg 2 hr after the end of restraint), cortical [3H]ketanserin binding remained unaltered. Chlorisondamine treatment was inactive, except for the amplification of the head shake response to DOI (2 mg/kg) in restrained rats. When exposed to the social interaction test, neither restraint nor chlorisondamine affected social interaction, locomotion, or rearings. In the elevated plus-maze, the percent number of open arms entered and the total number of arms entered were decreased by acute restraint, whilst chlorisondamine pretreatment was inactive.
Chaouloff
F
F
Laboratoire de Pharmacologie, Groupe de Neuropharmacologie, CNRS, CHU Necker, Paris, France.
Baudrie
V
V
Coupry
I
I
D000818:Animals; D001007:Anxiety / Q000523:psychology*; D001522:Behavior, Animal / Q000187:drug effects*; D001835:Body Weight / Q000187:drug effects / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002714:Chlorisondamine / Q000494:pharmacology*; D007398:Interpersonal Relations; D007650:Ketanserin / Q000493:pharmacokinetics*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D012149:Restraint, Physical; D013315:Stress, Psychological / Q000378:metabolism*; D014364:Tryptophan / Q000378:metabolism
D011985:Receptors, Serotonin; D014364:Tryptophan; D007650:Ketanserin; D002714:Chlorisondamine