The Neurotensin NTS1 Receptor Agonist PD149163 Produces Antidepressant‐Like Effects in the Forced Swim Test: Further Support for Neurotensin as a Novel Pharmacologic Strategy for Antidepressant Drugs

Preclinical Research

Neurotensin is a nonbrain penetrant neuropeptide neurotransmitter that alters dopaminergic and serotonergic neurotransmission. Previous animal behavioral studies have demonstrated that intra‐ventral tegmental administration of neurotensin and system administration of the selective neurotensin NTS₁ receptor agonist, PD149163 produce antidepressant‐like effects in a forced swim test and a differential reinforcement of low rate task, respectively. The present study sought to expand upon these past findings by assessing systemic administration of PD149163 in a forced swim test, a primary antidepressant preclinical screening model, in mice. The tricyclic antidepressant drug imipramine was tested for comparison, and both compounds were also assessed in an open field test. Both PD149163 and imipramine reduced time spent immobile, an antidepressant‐like effect, in the forced swim test. The highest dose of each compound significantly reduced locomotor activity. These findings provide further evidence for the putative antidepressant effects for PD149163 and suggest that NTS₁ receptor activation may be a novel pharmacologic strategy for antidepressant drug development. Drug Dev Res 78 : 196–202, 2017. © 2017 Wiley Periodicals, Inc.