Effects of pentylenetetrazol-induced kindling of seizures on rat emotional behavior and brain monoaminergic systems.
The influence of pentylenetetrazol (PTZ)-induced kindling of seizures on the rat emotional behavior, the brain monoamine turnover rate measured in vitro, and correlation between behavioral and biochemical parameters, were examined in rats. The repeated administration of PTZ (35 mg/kg, ip) evoked kindled seizures in rats (Stage 4 or 5 of clonic-tonic convulsions-maximum). PTZ kindling caused selective changes in the rat emotional behavior, present in some models of anxiety only (a decreased freezing time in the conditioned freezing test and a decreased spontaneous and aversively conditioned ultrasonic vocalization). Simultaneously, PTZ kindling decreased the concentration of homovanillic acid (HVA) and 5-hydroxyindoleacetic acid (5-HIAA) in the prefrontal cortex, decreased the DA (HVA/DA ratio) turnover rate in the striatum, and inhibited the serotonin (5-HT) metabolism (5-HIAA/5-HT ratio) in the hippocampus and the prefrontal cortex. Correlations between dopamine (DA) or 5-HT regional metabolic rates in brain structures and animal behavior were either abolished or reversed in PTZ-kindled animals. It is concluded that both DA and 5-HT systems contribute to the emotional effects of PTZ-induced kindling of seizures. The hypothesis is put forward that PTZ kindling-induced inhibition of the serotonergic innervation may lead to the compensatory increase in 5-HT(1A) receptors in the dentate gyrus of the hippocampus, thus evoking the anxiolytic-like changes in animal behavior.
Szyndler
Janusz
J
Department of Experimental and Clinical Pharmacology, Medical University, Krakowskie Przedmieście 26/28, 00-927, Warsaw, Poland.
Rok
Paulina
P
Maciejak
Piotr
P
Walkowiak
Jerzy
J
Członkowska
Agnieszka I
AI
Sienkiewicz-Jarosz
Halina
H
Wisłowska
Aleksandra
A
Zienowicz
Małgorzata
M
Lehner
Małgorzata
M
Bidziński
Andrzej
A
Kostowski
Wojciech
W
Plaznik
Adam
A
D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D003213:Conditioning, Psychological / Q000187:drug effects / Q000502:physiology; D004644:Emotions / Q000187:drug effects* / Q000502:physiology; D007696:Kindling, Neurologic / Q000187:drug effects* / Q000502:physiology; D008297:Male; D010433:Pentylenetetrazole / Q000494:pharmacology* / Q000633:toxicity; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced* / Q000378:metabolism; D014828:Vocalization, Animal / Q000187:drug effects / Q000502:physiology
D015306:Biogenic Monoamines; D010433:Pentylenetetrazole