The Female Urine Sniffing Test: A Novel Approach for Assessing Reward-Seeking Behavior in Rodents

Malkesman, Oz; Scattoni, María Luisa; Paredes, Daniel; Tragon, Tyson; Pearson, Brandon L.; Shaltiel, Galit; Chen, Guang; Crawley, Jacqueline N.; Manji, Husseini K.

doi:10.1016/j.biopsych.2009.10.018

Cited by 172 publications

(151 citation statements)

References 52 publications

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“…Also, HPA axis function was severely disrupted in experiment 1, with an increase in corticosterone release and diminished feedback recovery after an acute stressor (Bartolomucci et al, 2005; Schmidt et al, 2010). We were able to replicate several behavioral phenotypes that have been frequently described, such as disturbed exploratory and social behavior as well as increased anxiety-related and anhedonic behavior (Choleris et al, 2001;Hartmann et al, 2012;Malkesman et al, 2010).…”

Section: Discussionmentioning

confidence: 90%

Differences in FKBP51 Regulation Following Chronic Social Defeat Stress Correlate with Individual Stress Sensitivity: Influence of Paroxetine Treatment

Wagner

Marinescu

Hartmann

et al. 2012

Neuropsychopharmacol

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Various clinical studies have identified FK506-binding protein 51 (FKBP51) as a target gene involved in the development of psychiatric disorders such as depression. Furthermore, FKBP51 has been shown to affect glucocorticoid receptor signaling by sensitivity modulation and it is implicated in stress reactivity as well as in molecular mechanisms of stress vulnerability and resilience. We investigated the physiological, behavioral, and neuroendocrine parameters in an established chronic stress model both directly after stress and after a recovery period of 3 weeks and also studied the efficacy of paroxetine in this model. We then examined FKBP51 mRNA levels in the dorsal and ventral part of the hippocampus and correlated the expression to behavioral and endocrine parameters. We show robust chronic stress effects in physiological, behavioral, and neuroendocrine parameters, which were only slightly affected by paroxetine treatment. On the contrary, paroxetine led to a disruption of the neuroendocrine system. FKBP51 expression was significantly increased directly after the stress period and correlated with behavioral and neuroendocrine parameters. Taken together, we were able to further elucidate the role of FKBP51 in the mechanisms of stress resilience and vulnerability, especially with respect to behavioral and neuroendocrine parameters. These findings strongly support the concept of FKBP51 as a marker for glucocorticoid receptor sensitivity and its involvement in the development of psychiatric disorders.

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Section: Discussionmentioning

confidence: 90%

Differences in FKBP51 Regulation Following Chronic Social Defeat Stress Correlate with Individual Stress Sensitivity: Influence of Paroxetine Treatment

Wagner

Marinescu

Hartmann

et al. 2012

Neuropsychopharmacol

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“…Female urine sniffing test-A separate cohort of mice was treated with the same chronic corticosterone administration paradigm as described above but assessed for female urine sniffing preference as a measure of hedonic behaviour 35 . Mice were singly-housed in freshly-made home cages for a habituation period of 10 min.…”

Section: Chronic Corticosterone-induced Anhedoniamentioning

confidence: 99%

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

Zanos¹

2017

European Neuropsychopharmacology

254

692

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Author Contributions: PZ, RM, PJM, IWW, CJT, CAZ, and TDG were responsible for the overall experimental design. PJM, YF, and CJT synthesised the ketamine metabolites and deuterated ketamine derivatives, and provided mass spectrometer confirmations. Bioanalytical quantitation of ketamine and metabolites were performed by RM, NSS, and KSSD. PZ, PG, and HJP conducted and analysed the results of the behavioural and EEG experiments. XPH supervised and analysed the results of the binding experiments. PY performed the western blot experiments. EXA, MA, JF, and SMT helped design and analyze the electrophysiology experiments, which were conducted by MA, JF, and SMT. GIE and CLM conducted and analysed the results of the i.v. self-administration. PZ and TDG outlined and wrote the paper, which was reviewed by all authors.The authors declare competing financial interests: IWW, RM, and CAZ are listed as co-inventors on a patent for the use of (2R,6R)-hydroxynorketamine, (S)-dehydronorketamine and other stereoisomeric dehydro-and hydroxylated metabolites of (R,S)-ketamine metabolites in the treatment of depression and neuropathic pain. IWW, CAZ, RM, TG, PZ, CT, and PM are listed as co-inventors on a patent application for the use of (2R,6R)-hydroxynorketamine and (2S,6S)-hydroxynorketamine in the treatment of depression, anxiety, anhedonia, suicidal ideation and post-traumatic stress disorders. IWW, CAZ, RM, CT, and PM have assigned their patent rights to the U.S. government but will share a percentage of any royalties that may be received by the government. TG and PZ have assigned their patent rights to the University of Maryland Baltimore but will share a percentage of any royalties that may be received by the University of Maryland Baltimore. All other authors declare no competing interests. HHS Public Access AbstractMajor depressive disorder afflicts ~16 percent of the world population at some point in their lives. Despite a number of available monoaminergic-based antidepressants, most patients require many weeks, if not months, to respond to these treatments, and many patients never attain sustained remission of their symptoms. The non-competitive glutamatergic N-methyl-D-aspartate receptor (NMDAR) antagonist, (R,S)-ketamine (ketamine), exerts rapid and sustained antidepressant effects following a single dose in depressed patients. Here we show that the metabolism of ketamine to (2S,6S;2R,6R)-hydroxynorketamine (HNK) is essential for its antidepressant effects, and that the (2R,6R)-HNK enantiomer exerts behavioural, electroencephalographic, electrophysiological and cellular antidepressant actions in vivo. Notably, we demonstrate that these antidepressant actions are NMDAR inhibition-independent but they involve early and sustained α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptor activation. We also establish that (2R,6R)-HNK lacks ketamine-related side-effects. Our results indicate a novel mechanism underlying ketamine's unique antidepressant properties, which involves the required activity of a dist...

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“…The female urine-sniffing test (FUST) is based on the attraction of male rodents to pleasurable pheromones in urine and serves as a measure of rewardseeking behavior (30). For FUST, the mice are first exposed to a cotton tip dipped in water and then exposed to another cotton tip with fresh urine collected from same-strain females.…”

Section: M1-achr Mediates Cholinergic Stimulation Of Sst Interneuronsmentioning

confidence: 99%

GABA interneurons mediate the rapid antidepressant-like effects of scopolamine

Wohleb¹,

Wu²,

Gerhard³

et al. 2016

Journal of Clinical Investigation

129

112

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R e s e a R c h a R t i c l e2 4 8 2 jci.org Volume 126 Number 7 July 2016 IntroductionMajor depressive disorder (MDD) is a recurring neuropsychiatric illness that affects up to 17% of the population and causes substantial social and economic burdens (1-4). While some patients respond to existing medications, currently available antidepressants take weeks to months to have an effect, and many patients are considered treatment resistant because they fail to respond to 2 or more antidepressants (5). Recent studies demonstrate that scopolamine, a nonselective muscarinic acetylcholine (ACh) receptor (mAChR) antagonist, and ketamine, an NMDA receptor antagonist, produce rapid antidepressant actions (within hours) and are effective even in treatment-resistant MDD patients (6-8). The rapid antidepressant actions of scopolamine and ketamine are dependent on glutamate release and induction of new spine synapses in the medial prefrontal cortex (mPFC) (9-11), effects that directly target the synaptic pathophysiology of MDD and chronic stress (12-19). However, a major question in the field is, what are the initial cellular targets that mediate the increase in glutamate transmission, leading to increased synapse formation and rapid antidepressant behavior (10, 20, 21)? One hypothesis is that scopolamine blocks muscarinic receptors on GABAergic interneurons, resulting in disinhibition of pyramidal neurons and increased glutamate transmission. Alternatively, scopolamine may act directly on pyramidal neurons to enhance synaptic plasticity and produce antidepressant behavioral responses. Recent studies suggest that the M1-type muscarinic ACh receptor (M1-AChR) subtype may mediate the antidepressant actions of scopolamine (9, 22, 23).M1-AChRs are expressed on both GABAergic interneurons and glutamatergic pyramidal neurons in the mPFC and regulate the activity of both cell types (24)(25)(26).In the present study, we used transgenic mice and viralmediated gene transfer to drive Cre-dependent expression of M1-AChR shRNA in different subtypes of GABA interneurons or glutamate neurons in the mPFC. The results demonstrate that M1-AChR knockdown in GABA interneurons, but not pyramidal neurons, blocks the antidepressant-like response to scopolamine in mouse behavioral models. In addition, we show that knockdown of M1-AChR in somatostatin (SST), but not parvalbumin (PV), interneurons, blocks the actions of scopolamine. These findings reveal that M1-AChRs on SST interneurons in the mPFC are a critical cellular target underlying the rapid antidepressant effects of scopolamine. Results CaMKII+ and GAD + cell type-specific knockdown of M1-AChR in the mPFC. To determine whether glutamatergic pyramidal neurons and GABAergic interneurons in the mPFC express M1-AChR, double immunohistology was conducted with an M1-AChR antibody and Ca 2+ /calmodulin-dependent kinase II (CaMKII; pyramidal cell) or glutamate decarboxylase-67 (GAD67; GABA interneuron) (25). The results show that CaMKII + pyramidal neurons display punctate M1-AChR labeling in the mPF...

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The Female Urine Sniffing Test: A Novel Approach for Assessing Reward-Seeking Behavior in Rodents

Cited by 172 publications

References 52 publications

Differences in FKBP51 Regulation Following Chronic Social Defeat Stress Correlate with Individual Stress Sensitivity: Influence of Paroxetine Treatment

Differences in FKBP51 Regulation Following Chronic Social Defeat Stress Correlate with Individual Stress Sensitivity: Influence of Paroxetine Treatment

NMDAR inhibition-independent antidepressant actions of ketamine metabolites

GABA interneurons mediate the rapid antidepressant-like effects of scopolamine

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