The four-plates test–retest paradigm to discriminate anxiolytic effects

Abstract

Anxiogenic behaviour on retesting indicates aversive learning. The protocol test-retest is unable to discriminate between the anxiolytic effect of BZDs from that of paroxetine or venlafaxine. However, this modified model may constitute a new tool to investigate other neural pathways implicated in anxiety.

Phf8 loss confers resistance to depression-like and anxiety-like behaviors in mice

“…In agreement with this observation, we find that PHF8 is abundantly expressed in structures of the forebrain that are known to contribute to resilience toward anxiety and depression including the prefrontal cortex, ventral striatum and hippocampus3435363741. Critically, our RNA-Seq and ChIP-qPCR data provide a direct mechanistic link between the lack of PHF8 and elevated expression of serotonin receptors including 5-HT1A, 5-HT1B and 5-HT2A.…”

“…Inspection of differentially expressed genes in the prefrontal cortex of Phf8 KO mice revealed upregulation of multiple serotonin receptors including Htr1b, Htr2a and Htr1a, which have previously been linked to anxiety and depressive phenotypes in rodents34353637 (Fig. 5d).…”

“…Third, postmortem tissue from suicide victims shows reduced HTR1B mRNA levels within prefrontal cortex and hippocampus44. Fourth, mice deficient for Htr1a display increased anxiety- and depression-like behaviours34, whereas treatment of rodents with 5-HT1A, 5-HT1B or 5-HT2A agonists have similar anti-anxiety effects35363745.…”

Psychedelics

“…DOI was first shown to possess an anxiolytic effect in this model by Nic Dhonnchadha et al (2003). Subsequently, Ripoll et al (2005) assessed the ability of the four-plates to distinguish the anxiolytic effect of DOI from diazepam, alprazolam, paroxetine, and venlafaxine. In contrast with the other drugs, DOI was the only one able to restore the number of punished crossings to the same value seen in naïve saline-treated mice.…”

Selective effects of benzodiazepines on the acquisition of conditioned taste aversion compared to attenuation of neophobia in C57BL/6 mice

“…The amygdala is one brain region where inhibitory effects of benzodiazepines on passive avoidance acquisition are mediated, since midazolam injected into the amygdala before training impairs acquisition of passive avoidance (Dickinson-Anson and McGaugh 1993). Interestingly, in a four-plate test-retest procedure, mice injected with low-dose diazepam prior to conditioning displayed similar behavior (reduction in number of punished passages on retest trial) as vehicle-treated mice (Ripoll et al 2005), indicating a passive avoidance acquisition. However, further retests as follow-up for extinction were not performed.…”