Effects of Riluzole and Gabapentin on Learning, Anxiety and Social Behaviors in Autism-like Rat Model
Background: Autism spectrum disorder (ASD), is a neurodevelopmental disorder, characterized by difficulties in social interaction and communication and as well as repetitive and ritualistic behaviors. Despite the burden of the ASD on individual, family and community is high, no specific causes and optimal treatment modalities have not been identified yet. Dysfunction in the glutamatergic and GABAergic systems contributing the neurobiology of ASD have recently been proposed.
Objectives: We aimed to investigate effects of the riluzole, an antiglutamate agent, and gabapentin which increases GABAergic transmission, on learning, anxiety and social behaviors in autism-like rat model.
Methods: On the 12.5th gestational day, valproic acid was applied parenterally to the female Wistar Albino rats, except for the autism-negative control group, to create autism-like model (ALM). Newborn male rat pups (n=40) divided into 5 equal groups; negative control, ALM-nontreated (sham control), ALM+ riluzole treated, ALM + gabapentin treated, and ALM + combination of gabapentin & riluzole treated (n=8). Riluzole (10 mg/kg/day p.o) and gabapentin (300 mg/kg/day p.o.) were administered via orogastric gavage in the 3rd postnatal week for 2 weeks. Behavioral tests, Morris water maze (MWM), open field test (OFT) and three-chambered social approach test (TSAT) were applied in the 6th postnatal week.
Results: Both sociability and social preference indices with strangers in TSAT were lower in the ALM rats than the negative groups (p<0.01) indicating that the model was well fitted. Among the drug groups, combined treated rats showed the highest sociability index and social preference index (p<0.01). In the OFT, riluzole treated group had spent more rearing behaviors and spent less time in the outer squares (periphery) (p<0.05). Gabapentin treated rats showed the least rearing and grooming behaviors in the OFT. In the MWM test, the percent of the time spent in the previously learned platform was the highest in the riluzole only group (p<0.05) and this learning was the worst in the gabapentin treated rats (p>0,05).
Conclusions: All these results suggest that riluzole, an antiglutamatergic agent, seems to have some possible positive effects on social interaction, anxiety level and spatial learning in an autism-like rat model. If gabapentin is used alone, limitedly play a positive role on social behavior whereas a negative role in learning. However gabapentin may attenuate the social behaviors in combined treatment. Gabapentin may also decrease exploratory motions as well as anxiety levels. Further molecular and biochemical studies are needed to reveal the underlying etiological and therapeutic mechanisms of these neurotransmitter modulators.