The role of technical, biological and pharmacological factors in the laboratory evaluation of anticonvulsant drugs. VI. Seasonal influences on maximal electroshock and pentylenetetrazol seizure thresholds.

Abstract

There is strong evidence for circadian rhythmicity in certain seizure types, whereas only a few studies have addressed the possibility of seasonal rhythms in convulsive activity. In the present experiments, seizure thresholds to different types of seizures were determined twice per month over a period of 13 months in mice under controlled environmental conditions, i.e., constant photoperiod, temperature, humidity, and food. Each group of animals was used for only one experiment, and the age of the mice used per month was the same throughout the study. Furthermore, all experiments were done at the same time in the morning to avoid circadian variation. Thresholds for the following seizure types were determined: (1) tonic hindlimb seizures induced by electrical (transauricular) stimulation; (2) myoclonic seizures induced by intravenous (i.v.) infusion of pentylenetetrazol (PTZ); (3) generalized clonic seizures in response to i.v. PTZ; and (4) tonic forelimb seizures induced by PTZ. A significant seasonality was determined for myoclonic and clonic PTZ seizure thresholds with highest thresholds between February and April and lowest thresholds between July and September. No clear seasonality was seen for chemically or electrically induced tonic seizures. Determination of plasma corticosterone did not disclose any seasonal rhythm in adrenal corticosteroid production that resembled the circannual variation in myoclonic and clonic seizure thresholds. In conclusion, our experiments suggest the existence of seasonal rhythms in PTZ seizure thresholds in laboratory animals despite standardized environmental conditions. A possible explanation for the findings may be the known seasonal alteration of the geomagnetic field which, by its effect on the pineal production of melatonin, may act as a seasonal synchronizor ("zeitgeber") in animals in the absence of other synchronizing forces, such as seasonal changes in photoperiod and ambient temperature.