Behavioral and neurochemical alterations following intracerebroventricular administration of anti-serotonin antibodies in adult Balb/c mice.
The effects of intracerebroventricular injections of serotonin (5-HT) antibodies were studied for changes in 5-HT, dopamine (DA), their metabolites and norepinephrine (NE) as well as 5-HT mediated behavior in adult mice. While nociceptive thresholds (tail-flick latency) were inhibited in antibody treated animals, tremor response to 5-methoxy-N,N-dimethyl tryptamine administration was increased. 5-HT and DA in the nucleus raphe dorsalis (NRD), substantia nigra (SN), nucleus caudatus putamen (NCP) and in the substantia grisea centralis, and NE in the former two nuclei were significantly decreased in these animals. 5-Hydroxyindoleacetic acid was unaffected in all nuclei except NRD, where it was inhibited. Homovanillic acid and 3,4-dihydroxyphenylacetic acid were inhibited in all nuclei except in NCP. The brunt of insult was more evident in NRD and SN where all neurotransmitters were inhibited for a longer period. 5-HT turnover was increased in all the nuclei, however only SN showed increased DA turnover. It may be assumed that the observed neurochemical and behavioral changes were the consequence of the antibodies binding to 5-HT, which in turn influenced the anatomically and functionally connected neurotransmitters. While the study contributes to the existing understanding of central neurotransmitter control on behavior, it fails to delineate the underlying mechanism. The possibility of developing a useful, drug-free 5-HT deficient animal model for studying clinical disorders, as well as for solving some of the basic questions related to the physiological functions of 5-HT in adult animals are envisaged from the study.
Division of Pharmacology and Experimental Therapeutics, Indian Institute of Chemical Biology, Calcutta.
S
S
Mohanty
H W
HW
Steinbusch
D K
DK
Ganguly
K P
KP
Mohanakumar
D000818:Animals; D000906:Antibodies / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D004298:Dopamine / Q000378:metabolism; D007276:Injections, Intraventricular; D051379:Mice; D008807:Mice, Inbred BALB C; D009638:Norepinephrine / Q000378:metabolism; D017288:Pain Threshold; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D011817:Rabbits; D011903:Raphe Nuclei / Q000187:drug effects / Q000378:metabolism; D012701:Serotonin / Q000276:immunology* / Q000502:physiology; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism
D000906:Antibodies; D012701:Serotonin; D004298:Dopamine; D009638:Norepinephrine