Acute, but not repeated, administration of the neurotensin NTS1 receptor agonist PD149163 decreases conditioned footshock-induced ultrasonic vocalizations in rats

Abstract

Neurotensin is an endogenous neuropeptide that has significant interactions with monoamine neurotransmitter systems. To date, neurotensin NTS1 receptor agonists, such as PD149163, have been primarily evaluated for the treatment for schizophrenia, drug addiction, and pain. Recently, PD149163 was found to attenuate fear-potentiated startle in rats, an experimental procedure used for screening anxiolytic drugs. The present study sought to extend these findings through testing PD149163 in a conditioned footshock-induced ultrasonic vocalization (USV) model. Conditioning was conducted in Male Wistar rats using chambers equipped with shock grid floors and an ultrasonic vocalization detector. PD149163 and the 5-HT1A receptor partial agonist buspirone produced a statistically significant reduction of 22 kHz USV counts. The typical antipsychotic haloperidol also reduced 22 kHz USV counts, but did so at cataleptic doses. Ten days of repeated administration of PD149163 abolished the inhibitory effects of PD149163 on 22 kHz USVs. These findings further support an anxiolytic profile for PD149163. However, tolerance to these effects may limit the utility of these drugs for the treatment of anxiety.

Repeated effects of the neurotensin receptor agonist PD149163 in three animal tests of antipsychotic activity: Assessing for tolerance and cross-tolerance to clozapine

“…Although repeated PD treatment reduced 22 kHz USVs, no tolerance was seen during challenge. These results contradicted those by Prus et al , 2013, where repeated PD administration decreased the number of conditioned footshock-induced 22 kHz USVs. Since the mentioned study administered PD 1.0 mg/kg for ten consecutive days, it is possible that the discrepancy is due to the longer time period required for tolerance to develop in 22 kHz USV-related behaviors.…”

Do the effects of prenatal exposure and acute treatment of methamphetamine on anxiety vary depending on the animal model used?

“…A USV anxiety model based on foot-shocks can be designed with different protocols. The procedures, which were used in our study, were adapted from previous USV studies [29,38,47].…”

Maternal Separation Enhances Conditioned Fear and Decreases the mRNA Levels of the Neurotensin Receptor 1 Gene with Hypermethylation of This Gene in the Rat Amygdala

“…NTS is an endogenous neuropeptide that closely interacts with monoamine neurotransmitter systems [16], and NTS receptor (NTSR) 1 and 2 are densely located in structures that are important for anxiety, including the amygdala (AMY) and hippocampus (HIP) [17]. The systemic administration of a NTSR1 agonist significantly decreased conditioned footshock-induced ultrasonic vocalization in rats [18], even while decreasing fear-potentiated startling in rats [19]. Moreover, NTSR1 knockout mice showed higher freezing rates than wild-type mice in contextual fear stress situations [11].…”