Systemic administration of the neurotensin NTS₁-receptor agonist PD149163 improves performance on a memory task in naturally deficient male Brown Norway rats.

Abstract

Agonists for neurotensin NTS1 receptor consistently exhibit antipsychotic effects in animal models without producing catalepsy, suggesting that NTS1 receptor agonists may be a novel class of drugs to treat schizophrenia. Moreover, studies utilizing NTS1 agonists have reported improvements in some aspects of cognitive functioning, including prepulse inhibition and learning procedures, that suggest an ability of NTS1 receptor agonists to diminish neurocognitive deficits. The present study sought to assess both baseline delay-induced memory performance and the effects of NTS1 receptor activation on learning and memory consolidation in male Long Evans and Brown Norway rats using a delayed non-match to position radial arm maze task. In the absence of drugs, Brown Norway rats displayed a significant increase in spatial memory errors following a 3, 7, and 24 hour delay, whereas Long Evans rats exhibited an increase in spatial memory errors following only a 7 and 24 hour delay. With Brown Norway rats, administration of PD149163 before or after an information trial significantly reduced errors during a retention trial after a 24 hour delay. Administration of the NTS1/2 receptor antagonist SR142948 prior to the information trial did not affect retention trial errors. These data are consistent with previous findings that Brown Norway rats have natural cognitive deficits and that they may be useful for assessing putative antipsychotic drugs for cognitive efficacy. Moreover, this study supports previous findings suggesting that NTS1 receptor agonists may improve some aspects of cognitive functioning.

Song in an Affiliative Context Relates to the Neural Expression of Dopamine- and Neurotensin-Related Genes in Male European Starlings

“…Neurotensin (NT) is a candidate neuropeptide to modulate undirected song because it strongly interacts with dopaminergic signaling [Binder et al, 2001] and is implicated in social behavior [Driessen et al, 2014; Gammie et al, 2009; Merullo et al, 2015b; Merullo et al, 2015a] and learning [Azmi et al, 2006; Feifel et al, 2009; Keiser et al, 2014; Laszlo et al, 2010; Tirado-Santiago et al, 2006; Xiao et al, 2014]. NT and the NT1 receptor (NTR1; the only known avian NT receptor [Numao et al, 2011]) co-localize with DA neurons in the ventral tegmental area (VTA) and are also found in LS and Area X [Atoji et al, 1996; Binder et al, 2001; Merullo et al, 2015b; Merullo et al, 2015a; Xie et al, 2010].…”

ML314: A Biased Neurotensin Receptor Ligand for Methamphetamine Abuse

“…The peripheral administration of NTR1 peptide agonists produces behaviors exactly opposite the classical effects associated with psychostimulant abuse such as hyperactivity, cognitive deficits, psychotic episodes, and neurotoxicity. Importantly, NT peptides reverse meth induced hyperactivity, are cognitive enhancers 23 , display antipsychotic properties in animal models, and are neuroprotective 24-26 (for a comprehensive review see 27 ). In animal studies the NT peptide variant NT69L produced blockade of D-amphetamine induced locomotor activity and did not elicit tolerance 24, 28 .…”

A marine analgesic peptide, Contulakin-G, and neurotensin are distinct agonists for neurotensin receptors: uncovering structural determinants of desensitization properties

“…There are several BBB-penetrant NT analogs which exhibit analgesic activities following systemic administration, for example NT69L ( Boules et al, 2006 ), ANG2002 ( Demeule et al, 2014 ), or polyamine-NT ( Zhang et al, 2009 ). BBB-penetrant and NTS1-selective agonist, PD149163 ( Wustrow et al, 1995 ), was developed by Pfizer and is active in drug self-administration test ( Hanson et al, 2013 ) and in cognitive performance test ( Keiser et al, 2014 ). Another example of BBB-penetrant NT analog is the anticonvulsant NT-BBB-1, which was active in a pharmacoresistant model of epilepsy ( Green et al, 2010 ).…”