Neurotensin receptor-1 agonist PD 149163 modulates the lipopolysaccharide-induced behavioral disturbances in mice

Neuroendocrine-immune homeostasis is a prerequisite for neurobehavioral performances. Dysregulation of this homeostasis manifested in behavioral dysfunctions and neurodegenerative diseases, including schizophrenia and Parkinson's disease. The present study aimed to investigate the role of PD 149163 (PD), a neurotensin agonist, in the modulation of behavioral disturbances induced by lipopolysaccharide (LPS) in mice. Thirty-six female mice, 12 weeks old, were divided into 6 groups (n = 6/group). Group I (control) mice were given intraperitoneal (i.p.) injection of saline. Group II (LPS) received LPS (1 mg/kg, i.p.) for 5 days. Group III (LPS + PD Low) and IV (LPS + PD High) have received an injection of LPS (1 mg/kg, for 5 days) and after that treated with PD 100 µg/kg and 300 µg/kg, i.p., respectively, for 21 days. Group V (PD Low) and VI (PD High) were exposed to PD 100 µg/kg and 300 µg/kg, respectively, for 21 days.

In the open-field test, the PD attenuated the behavior of LPS-exposed mice by increasing the number of squares crossed, time spent in the central square, rearing and grooming, and decreasing immobility, latency and defecation. Likewise, in the elevated plus-maze test, PD increased the number of entries on open and enclosed arms, time spent on open and enclosed arms, grooming and rearing, and reduced the head dipping and immobility in LPS-challenged mice. The PD enhanced the immobility time in the forced swimming test, and sucrose consumption in the sucrose preference test decreased after LPS exposure.

This study suggests that PD modulates the LPS-induced anxiety and depression-like behavioral impairments and could be an alternate choice of the atypical antipsychotic drugs (AAPDs) in the future.