Taurine-Derived Compounds Produce Anxiolytic Effects in Rats Following Developmental Lead Exposure

Abstract

Lead (Pb²⁺) is a developmental neurotoxicant that disrupts the GABA-shift and subsequently causes alterations in the brain’s excitation-to-inhibition (E/I) balance. Taurine is a well-established neuroprotective and inhibitory compound for regulating brain excitability. Since mechanistically taurine can facilitate neuronal inhibition through the GABA-_AR, the present study examined the anxiolytic potential of taurine derivatives. Treatment groups consisted of the following developmental Pb²⁺-exposures: Control (0 ppm) and Perinatal (150 ppm or 1,000 ppm lead acetate in the drinking water). Rats were scheduled for behavioral tests between postnatal days (PND) 36–45 with random drug assignments to either saline, taurine, or taurine-derived compound (TD-101, TD-102, or TD-103) to assess the rats’ responsivity to each drug in mitigating the developmental Pb²⁺-exposure and anxiety-like behaviors through the GABAergic system. Long-Evans hooded rats were assessed using an open field (OF) test for preliminary locomotor assessment. Twenty-four hours later, the same rats were exposed to the elevated plus maze (EPM) and were given an i.p. injection of 43 mg/Kg of the saline, taurine, or TD drugs 15 min prior to testing. Each rat was tested using the triple-blind random assignment method for each drug condition. The OF data revealed that Control female rats had increased locomotor activity over Control male rats, and the Pb²⁺-exposed males and females had increased locomotor activity when compared to the Control male and female rats. However, in the EPM, the Control female rats exhibited more anxiety-like behaviors over Control male rats, and the Pb²⁺-exposed male and female rats showed selective responsivity to TD drugs when compared to taurine. For Pb²⁺-exposed males, TD-101 showed consistent recovery of anxiety-like behaviors similar to that of taurine regardless of Pb²⁺ dose, whereas in Pb²⁺-exposed females TD-101 and TD-103 showed greater anxiolytic responses in the EPM. The results from the present psychopharmacological study suggests that taurine and its derivatives are interesting drug candidates to explore sex-specific mechanisms and actions of taurine and the associated GABAergic receptor properties by which these compounds alleviate anxiety as a potential behavioral pharmacotherapy for neurodevelopmental Pb²⁺ exposure.