Dopamine characteristics in rat genotypes with distinct susceptibility to epileptic activity: apomorphine-induced stereotyped gnawing and novelty/amphetamine-induced locomotor stimulation

Abstract

Rat genotypes differ in their susceptibility to spontaneously occurring spike-wave discharges and in their dopaminergic properties. In a previous study, it was found that spike-wave discharge incidence decreased in the following order in four rat genotypes during baseline and following injection with the dopamine antagonist haloperidol: apomorphine-susceptible (APO-SUS) > WAG/Rij > apomorphine-unsusceptible (APO-UNSUS) and ACI rats. The question in the present study was to what extent certain dopaminergic properties are pathognomonic for epileptic rats. Therefore, behavioral responses were assessed in order to investigate the dopaminergic properties in the four rat genotypes. Apomorphine-induced gnawing data imply that the dopamine activity of the nigrostriatal system in the WAG/Rij rats is higher than in APO-SUS but lower than in the ACI and APO-UNSUS rats. Furthermore, in previous studies APO-SUS have been shown to have a higher novelty/amphetamine-induced locomotion, indicative of a higher dopamine reactivity of the mesolimbic system as compared to APO-UNSUS rats. Results from the present study showed that WAG/Rij rats have a higher locomotor responsiveness to novelty/amphetamine, indicating a higher dopamine reactivity of the mesolimbic system in comparison to the ACI rats. It is suggested that the functional dopaminergic mesolimbic dominance is an important factor in the susceptibility to show spontaneously occurring spike-wave discharges.

Antidepressants but not antipsychotics have antiepileptogenic effects with limited effects on comorbid depressive‐like behaviour in theWAG/Rij rat model of absence epilepsy

“…Drug doses were chosen according to previous publications with chronic (long term) treatment not inducing side effects and with an effect on seizures (de Bruin et al ., ; Jakus et al ., ; Dobryakova et al ., ; Citraro et al ., ); furthermore, such doses are strongly linked to the doses used in patients. Drug metabolism and elimination is in most cases more efficient (faster) in rodents than in humans and, therefore, in most cases, the final dose used in rats is apparently much higher than the one used in clinical practice for patients.…”

“…Drug doses were chosen according to previous publications; with chronic (long term) treatment no obvious side effects were reported and effects on seizures were reported (de Bruin et al ., ; Jakus et al ., ; Dobryakova et al ., ; Citraro et al ., ); furthermore, such doses are representative of the doses used in patients (see Discussion and conclusions).…”

Sexual performance and precontact 50-kHz ultrasonic vocalizations in WAG/Rij rats: Effects of opioid receptor treatment

“…High levels of 50-kHz vocalizations are observed after amphetamine and D2 and D3 receptor stimulation in the nucleus accumbens [16][17][18][19][20]. The dopaminergic systems differ in WAG/Rij rats -they display lower activity of the nigrostriatal system and higher activity of the mesolimbic system in behavioral tests [1,57], with elevated levels of D2 receptors in the nucleus accumbens [58,59]. A high level of mesolimbic dopaminergic activity could feasibly correspond to a high level of PVs in WAG/Rij rats in our experiment.…”

Neurochemical and Behavioral Features in Genetic Absence Epilepsy and in Acutely Induced Absence Seizures

“…WAG/Rij rats showed also both a larger novelty and amphetamine induced increase in total distance moved than ACI rats in a brightly lit open field [310]. This novelty/amphetamine-induced ambulation score was interpreted as an index of the reactivity of the DA system in the mesolimbic system [313–315].…”