Neurochemical responses to antidepressants in the prefrontal cortex of mice and their efficacy in preclinical models of anxiety-like and depression-like behavior: a comparative and correlational study

Abstract

Although marble burying and forced swimming behavior have strong predictive validity in tests of antidepressant action, each assay appears to be underpinned by entirely different neurochemical systems.

S32212, a Novel Serotonin Type 2C Receptor Inverse Agonist/α2-Adrenoceptor Antagonist and Potential Antidepressant: II. A Behavioral, Neurochemical, and Electrophysiological Characterization

“…Potential antidepressant properties of S32212 were evaluated in a range of procedures, including the forced-swim test in rats, a procedure thought to model despair (Kobayashi et al, 2008;Carr and Lucki, 2011). Its effects were also evaluated in marble burying and isolation-induced aggression tests in mice, two empirical procedures responsive to currently available antidepressants Kobayashi et al, 2008).…”

“…Its effects were also evaluated in marble burying and isolation-induced aggression tests in mice, two empirical procedures responsive to currently available antidepressants Kobayashi et al, 2008). Psychomotor retardation can be pharmacologically mimicked by the administration of ␣ 2 -AR agonists, which provokes a loss of righting reflex (LRR) abolished not only by drugs possessing antagonist actions at ␣ 2 -ARs, but also by most clinically active antidepressants (Millan et al, , 2001Buyukdura et al, 2011).…”

“…The one-way ANOVA performed on D2 scores was as follows: F 3,44 ϭ 3.1; P Ͻ 0.05. ଙ indicates significance of differences to vehicle values in Dunnett's test; P Ͻ 0.05. generally attributed to antidepressant properties and were expressed by S32212 both subchronically and, in contrast to certain antidepressants such as SSRIs, acutely (Millan et al, 2001;Cryan et al, 2005;Millan, 2006;Kobayashi et al, 2008;Carr and Lucki, 2011). S32212 inhibited spontaneous marble burying in mice over a similar dose range: although not of any obvious construct validity for depressed states, suppression of marble burying may be related to the influence of SSRIs and tricyclics on compulsive behaviors (Millan et al, 2001;Kobayashi et al, 2008;Thomas et al, 2009).…”

“…ଙ indicates significance of differences to vehicle values in Dunnett's test; P Ͻ 0.05. generally attributed to antidepressant properties and were expressed by S32212 both subchronically and, in contrast to certain antidepressants such as SSRIs, acutely (Millan et al, 2001;Cryan et al, 2005;Millan, 2006;Kobayashi et al, 2008;Carr and Lucki, 2011). S32212 inhibited spontaneous marble burying in mice over a similar dose range: although not of any obvious construct validity for depressed states, suppression of marble burying may be related to the influence of SSRIs and tricyclics on compulsive behaviors (Millan et al, 2001;Kobayashi et al, 2008;Thomas et al, 2009). By analogy to marble burying, suppression of aggressive behavior in isolated mice is an empirical screen not easily related to core deficits of depression, despite the high incidence of aggression and irritability in patients (Millan et al, 2001;Millan, 2006;Dekeyne et al, 2008;Malkesman et al, 2009).…”

Physical Properties of Bedding Materials Determine the Marble Burying Behavior of Mice (C57BL/6J)

“…It was recently reported that the marble burying test simply reflects digging and other related behaviors [14][15][16][17], calling into question the validity of this behavior for assessing anxiety, defensiveness, compulsiveness, and so on. However, marble burying behavior correlates well with both serotonin (5-HT) transporter (SERT) binding of selective 5-HT reuptake inhibitors (SSRIs) and extracellular 5-HT levels in brains treated with SSRIs [18,19], and thus the behavior may reflect a relation between 5-HT neuronal *Address correspondence to this author at the Support Unit for Animal Experiments, Research Resources Center, Brain Science Institute, RIKEN, 2-1 Hirosawa, Wako-city, Saitama, 351-0198, Japan; Tel: +81-48-467-7659; Fax: +81-48-467-6287; E-mail: kaz-yamada@brain.riken.jp activity and anxiety, defensiveness, compulsiveness. Therefore, the marble burying test is often used to assess the efficacy of drugs such as SSRIs.…”