The endocannabinoid effect on sociability
Early life seizures in rodents leads to autistic-like behavior, characterized by low preference for novelty, deficit in social recognition and high anxiety. We used this animal model to better understand the role of the endocannabinoid system on sociability. Male Wistar rats at postnatal day 9 were subjected to pilocarpine-induced neonatal status epilepticus and controls received saline. From P60 groups received vehicle or JZL195 2 hours prior each behavioral test, in order to increase endocannabinoids availability. In social discrimination test, untreated control animals spent higher time with social novelty as compared to familiar one (t= 3.263; p<0.01). The JZL195 reduced the overall time spent with the conspecifics (F(1,19)=6.11; p=0.023) and also inhibited the social discrimination (t=0.17; p>0.05). In this paradigm, the significant interaction between factors (conspecific x treatment) (F(1,19)= 4.863;p=0.04) suggests that control animals under JZL195 effect exhibited reduced social motivation. In contrast, the untreated experimental group did not show preference for social novelty (t= 0.336; p>0.05) and JZL195 did not modify the impaired social discrimination. In social recognition test, control animals, regardless the treatment, showed habituation to the social stimulus (F(2,32)= 11.64, p=0.0002), suggesting that animals exhibited social recognition memory, but it was reduced by the treatment with JZL 195 (F(1,16)= 5.086, p= 0.038). Moreover, time of investigation increased when the familiar social stimulus was replaced by new one (F(1,16)=10.24, p=0.005), suggesting that social memory recognition was preserved. Treated control animals exhibited a lower time of investigation toward social stimulus (F(1,16)=9.092, p=0.0082), suggesting that JZL195 reduced the social motivation without affect social recognition memory. In the experimental group, the time of investigation decreased when exposed to the same animal (F (2,34)=7.92, p=0.0015), suggestive that the social recognition was preserved and unaffected by the treatment with JZL195 (F(1,17)= 0.246; n.s). The JZL195 decreased the time of investigation only in control group (t=2.464, p= 0.025) to values that are similar to the experimental one. After behavioral tests, brain tissues were used for CB1 receptor quantification by Elisa and for gene expression by RT-PCR: no difference between control and experimental animals was detected. Our results state that increased endocannabinoid signaling reduces social motivation in intact rats and has no effect in animals submitted to early life seizures.