Allopregnanolone dual modulates the serotoninergic and GABAergic system in a rat aggression model

MB MULLE BERNEDO; S GARCÍA; V ASTORGA; R CABRERA

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2019

SAIC-SAFE- SAB-SAP-AACYTAL-NANOMED-ar-HCS.

The serotonergic system is involved in a wide variety of physiological and behavioral functions. Serotonergic axons have been shown to target GABAergic inhibitory neurons and vice-versa. Also, the serotonergic system is influenced by changes in plasma and brain levels of neuroactive steroids. Progesterone derivative, allopregnanolone (Allo) enhances GABAA receptors sensibility, acting as an allosteric modulator on the function of GABA. This receptor acts as heteroreceptor in serotoninergic neurons. Allo, also modulates negatively 5-HT3 receptors. This neurosteroid influences a wide range of behaviors, among others, like aggressive behavior in rodents. This work aimed to evaluate modulatory Allo effects in an aggressive behavior rat model. Male Sprague-Dawley rats 60 days old were used. On a postnatal day 60 (PND), the rats were cannulated in the 3rd ventricle (icv). On PND 66, the rats received once pCPA (300 mg/kg, i.p) injection in order to generate aggressive behavior. On PND 72, the rats were divided randomly into groups, 1) Allo; 2) Bicuculine (Bic)+Allo; 3) Bic 4) 5-HT 5) Allo+ 5-HT. Moreover, 30` before resident intruder test (RVI) receive the drug icv. The behavioral activity of all groups was video recorded and was analyzed by the researchers. Aggressive behavior was evaluated as the presence of tromping, bites, attempted mounts, and lateral threats (AB). We also measured non-social interaction (lying and sitting), social interaction (sniffing and grooming) and locomotor activity. All data were expressed as a mean+ SEM and analyzed by ANOVA I and Tukey post hoc test. Allo positively modulates the GABAergic system by decreasing aggressive behavior (p ≤0.05). This decrease was reversed by the blockage of this system with Bicuculin (p ≤0.01 ). The administration of 5HT icv did not modify the aggressive behavior induced by pCPA depletion. Moreover, the previous administration of Allo to 5HT icv significantly increased this behavior (p ≤ 0.01).We conclude that Allo is a neurosteroid modulator of aggressive behavior in rats. This modulatory effect would be mediated by GABAergic and serotonergic mechanisms oppositely, thus proposing a duality in its modulatory capacity not described above, for this type of aggressive behavior in rats.