Behavioural brain research
October 1, 2020
Dionisio A Amodeo, Omron Hassan, Landon Klein et al.
25 citations
Activating serotonin 2A (5-HT2A) receptors impairs behavioral flexibility in male mice, as measured by a probabilistic reversal learning task. The selective 5-HT2A agonist 25CN-NBOH increased the number of trials needed to reach criterion during reversal learning, while the broader agonist DOI alone did not. However, combining DOI with a 5-HT2C receptor antagonist (SER-082) also impaired reversal learning, suggesting that 5-HT2A and 5-HT2C receptors have opposing effects on this aspect of executive function. All groups performed similarly on the initial spatial discrimination, indicating that the impairment was specific to adapting to changing contingencies.
Journal of psychiatric research
July 1, 2025
Joris Kamp, Megan E Sikkink, Mahalah R Buell et al.
In mice with reduced Sp4 expression, a gene linked to schizophrenia in humans, restoring Sp4 in young adults partially corrected two schizophrenia-related behavioral deficits—prepulse inhibition and hypersensitivity to ketamine—but did not improve context memory. The SP4 gene is strongly associated with schizophrenia risk; human studies show that loss of one copy increases odds of schizophrenia by about 9-fold. These results suggest that Sp4 restoration in adulthood may reverse some but not all behavioral abnormalities, supporting further investigation of SP4 as a potential drug target.
Pharmacology, biochemistry, and behavior
September 1, 2016
Adam L Halberstadt, James Hyun, Michael A Ruderman et al.
N-allylnormetazocine (NANM) disrupts prepulse inhibition (PPI) of acoustic startle in mice, a measure of sensorimotor gating. Racemic NANM and its (+)-isomer produced dose-dependent PPI disruption (3-30 mg/kg), while the (-)-isomer had no effect. Blocking kappa opioid or sigma-1 receptors did not prevent this disruption, and a selective kappa agonist also had no effect on PPI. The findings indicate that NANM's effects on sensorimotor gating are mediated through the PCP site of the NMDA receptor, not through kappa or sigma-1 receptors, consistent with evidence that sigma-1 receptors are not linked to hallucinogenic or psychotomimetic effects.
Psychopharmacology
April 1, 2016
Adam L Halberstadt, Natalia Slepak, James Hyun et al.
Methoxetamine (MXE), a ketamine analog sold online, produces behavioral effects in rats that closely resemble those of other dissociative anesthetics like phencyclidine (PCP) and ketamine. In Sprague-Dawley rats, MXE disrupted prepulse inhibition (PPI) of acoustic startle at doses of 3 and 10 mg/kg, with a potency ranking (PCP > MXE > S-(+)-ketamine > NANM > R-(-)-ketamine) that matches their affinities for the PCP binding site on NMDA receptors. In the behavioral pattern monitor, 10 mg/kg MXE caused locomotor hyperactivity, reduced rearing, increased path roughness, and perseverative locomotion—effects similar to those of PCP. These findings indicate MXE acts as a dissociative drug with abuse potential comparable to PCP and ketamine.