Neuro-protective effects of carbamazepine on sleep patterns and head and body shakes in kainic acid-treated rats.
The aim of this work was to analyze the effect of carbamazepine (CBZ) on sleep patterns and on "head and body shakes" and to determine the role of serotonin (5-HT) in a model of kainic-induced seizures. Thirty male Wistar rats (280-300 g) were used for polygraphic sleep recording. After a basal recording, the rats were allocated into three groups: kainic acid-treated animals (KA; 10 mg/kg; n=10), carbamazepine-treated animals (CBZ; 30 mg/kg; n=10) and animals injected with KA 30 min after pretreatment with CBZ (CBZ+KA; n=10). Polygraphic recordings were performed for 10 h for 3 days, with the exception of the CBZ group, which were observed for 1 day. In order to measure the head and body shakes that occurred over that time, a behavioral assessment was performed in two additional groups of KA (n=10) and CBZ+KA (n=10) animals. After 10 h of behavioral assessment, the rats were sacrificed, and the levels of 5-HT and 5-hydroxy-indol-acetic acid (5-HIAA) were analyzed. We compared these findings with the results from a group of rats without pharmacological intervention (n=10). All of the recordings were performed from 08:00 to 18:00 h.


METHODS
the electrographic parameters, head and body shake counting and monoamine concentrations were analyzed by an ANOVA test. Differences of *p < or = 0.01 and **p < or = 0.001 were considered statistically significant. Our results showed that CBZ exerted a protective effect on sleep pattern alterations induced by KA, which when administered alone caused a complete inhibition of sleep for the first 10 h after administration. Although there was a reduction in the amount of sleep after the administration of KA in CBZ-pretreated animals, sleep inhibition was incomplete. In addition, CBZ decreased the frequency of head and body shakes by 60% as compared to KA. The 5-HT and 5-HIAA levels in the pons were increased in the KA and KA+CBZ groups. Our conclusion is that in addition to decreasing seizure intensity, CBZ facilitates the partial recovery of sleep. These results suggest that CBZ provides neuro-protective effects on sleep and against seizures.
Laboratorio de Neuroquímica, Departamento de Neurofisiología, Instituto Nacional de Rehabilitación, Mexico. alfa1360@yahoo.com.mx
Alfonso
A
Alfaro-Rodríguez
Rigoberto
R
González-Piña
Emilio
E
Arch-Tirado
Miriam
M
Carrasco-Portugal
Beatríz
B
Pérez-Guillé
Rosa Eugenia
RE
Soriano-Rosales
Krystell
K
Padilla-Martin
Rebeca
R
Uribe-Escamilla
Norma
N
Labra-Ruiz
D000818:Animals; D000927:Anticonvulsants / Q000008:administration & dosage / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002220:Carbamazepine / Q000008:administration & dosage / Q000494:pharmacology*; D007608:Kainic Acid; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy; D012701:Serotonin / Q000378:metabolism; D012890:Sleep / Q000187:drug effects*
D000927:Anticonvulsants; D020746:Calcium Channels, L-Type; D018696:Neuroprotective Agents; D012701:Serotonin; D002220:Carbamazepine; D007608:Kainic Acid