NK3 receptor agonism reinstates temporal order memory in the hemiparkinsonian rat

Abstract

Animals treated with unilateral 6-hydroxydopamine (6-ODHA) injections, an animal model of Parkinson's disease, exhibit deficits in memory for temporal order, but show intact novel object recognition. Since senktide, a potent neurokinin-3 receptor (NK3-R) agonist, has been shown to have promnestic effects in the aged rat and to alleviate scopolamine-induced impairment, the present study aimed to assess possible promnestic effects of senktide in the hemiparkinsonian rat model. Animals received unilateral 6-ODHA microinjections into the medial forebrain bundle. Two weeks later, they were randomly assigned to treatment with vehicle, 0.2, or 0.4mg/kg senktide. Temporal order memory and place recognition tests were conducted, locomotor activity and turning behavior were assessed in the open field and anxiety-related behavior was measured in the light–dark box. Treatments were administered 30min prior to behavioral testing with an interval of seven days between tests. The animals treated with 0.2mg/kg senktide exhibited temporal order memory, unlike the vehicle-treated group. No significant treatment effects were found in the open field and light–dark box. Administration of 0.2mg/kg senktide may influence the prefrontal cortex and hippocampus, leading to compensations for deficits in memory for temporal order.