Molecular and Behavioral Neuroprotective Effects of Clavulanic Acid and Crocin in Haloperidol-Induced Tardive Dyskinesia in Rats

Clavulanic acid (ClvA), a beta-lactamase inhibitor, is being explored for its significant neuroprotective potential. The effects of ClvA were assessed both individually and in combination with crocin (Cr), an antioxidant derived from saffron, in the context of tardive dyskinesia (TD). In rat haloperidol (Hp)-induced-TD (1 mg/kg, i.p. 21 days), the effects of ClvA (50, 100, 150 mg/kg) and Cr (10, 20, 40 mg/kg) were assessed via vacuous chewing movements (VCM) and tongue protrusion (TP). Striatal malondialdehyde (MDA) and glutathione (GSH) were measured spectrophotometrically. Based on the results, ClvA (100 mg/kg) and Cr (10 mg/kg) were determined with sub-effective doses. Glutamate transporter-subtype1 (GLT1), dopamine active transporter (DAT), vesicular monoamine transporter-type2 (VMAT2), Bax/Bcl2, cleaved Caspase3, phosphorylated AKT/AKT, IL1β, and TNFα levels were quantified using western blotting in sub-effective doses and their combination. The behavioral results of catalepsy and orofacial dyskinesia demonstrated model establishment. Hp decreased GLT1 (p