Effect of ketamine administration, alone and in combination with E-6837, on climbing behavior

Abstract

Some types of schizophrenia have been associated with repetitive movements lacking specific purpose, also known as stereotyped behavior. Dopamine agonists (D2) and noncompetitive N-methyl-D-aspartate receptor antagonists (e.g. ketamine) have been administered in rodent models to induce stereotyped behavior that resembles some motor symptoms of schizophrenia. Recently, a relationship has been found between 5-HT6 receptors (5-HT6Rs) and dopaminergic activity. The present study evaluates the effect of ketamine (5 and 10 mg/kg), alone and in combination with the 5-HT6R agonist E-6837, on the climbing behavior of male mice. Ketamine was administered with an acute (1 day) and subchronic (5 day) scheme. Later, these doses and schemes were combined with an acute scheme of E-6837 (5 and 10 mg/kg). With both the acute and the subchronic schemes, ketamine increased climbing behavior at a dose of 10 mg/kg, and this effect was reversed by E-6837 (at 5 and 10 mg/kg). The present results suggest that there is an interaction between N-methyl-D-aspartate and 5-HT6 receptors in the regulation of climbing behavior. Further research is necessary to provide more evidence on this interaction.

The 5-HT6R agonist E-6837 and the antagonist SB-271046 reverse the psychotic-like behaviors induced by ketamine

“…The current study found that KET increases scaling behavior, as reported previously, which was reversed by the acute injection of the 5-HT 6 agonist E-6837 (Briones-Aranda et al , 2016). Surprisingly, the antagonist SB-271046 also diminished the scaling behavior (current study).…”

“…In this sense, it is known that oral administration of the 5-HT 6 R agonists WAY-181187 or WAY-208466 induces a reduction of adjunctive drinking in the rat schedule-induced polydipsia, a phenomenon linked to a reduction in OCB (Schechter et al , 2008). In the same line, our group reported that the 5-HT 6 R agonist E-6837 decreases the scaling behavior of mice tested in the CT after being subjected to a subchronic KET regimen (Briones-Aranda et al , 2016). However, the 5-HT 6 R antagonist DNA-1184 decreases the OCB in the marble-burying test (MBT) (Partyka et al , 2016).…”

“…For instance, some reports show that KET increases anxiety levels in the open-field test (OFT), the elevated plus-maze (EPM) (de Carvalho et al, 2019;Wąsik et al, 2019) and the light/dark test (LDT) (Pitsikas et al, 2019). Similarly, subchronic administration of KET induces stereotyped movements in the climbing test (CT) (Briones-Aranda et al, 2016) and other behavioral tests (Zoupa et al, 2019;Radford et al, 2017).…”

Evaluation of Brain Targeting and Antipsychotic Activity of Nasally Administrated Ziprasidone Lipid–Polymer Hybrid Nanocarriers

“…In addition, IN administration showed a significant reduction in the crossed-squares number compared to the IV ZP solution ( p < 0.05). This improvement in antipsychotic activity could be correlated with the selective increase in glutamate and dopamine release in the prefrontal cortex, nucleus accumbens and striatum [ 53 , 54 ]. ZP may inhibit the 5-HT2A receptors on glutamatergic terminals, causing a spontaneous reduction in the stimulating effect of ketamine in the dopamine-glutamate pathway [ 55 , 56 ].…”

Utilization of Polymeric Micelles as a Lucrative Platform for Efficient Brain Deposition of Olanzapine as an Antischizophrenic Drug via Intranasal Delivery

“…The ketamine dose affects the animals' behavior as a result of its effect on the neurotransmitters. Ketamine-induced hyperlocomotion was produced by a selective increase in glutamate and dopamine release in the prefrontal cortex, nucleus accumbens and striatum [62,63]. Pretreated rats with OZ solution or OZ-PM with a dose of 2 mg/kg showed a significant decrease in the ketamine-induced hypermobility, which was indicated by decreases in the observed rats' mobility (p < 0.001).…”