5-Hydroxytryptamine-interacting drugs in animal models of anxiety disorders: More than 30 years of research

Griebel

European Journal of Pharmacology

2003

Self Cite

258

159

The Mouse Defense Test Battery was developed from tests of defensive behaviors in rats, reflecting earlier studies of both acute and chronic responses of laboratory and wild rodents to threatening stimuli and situations. It measures flight, freezing, defensive threat and attack, and risk assessment in response to an unconditioned predator stimulus, as well as pretest activity and postthreat (conditioned) defensiveness to the test context. Factor analyses of these indicate four factors relating to cognitive and emotional aspects of defense, flight, and defensiveness to the test context. In the Mouse Defense Test Battery, GABA A -benzodiazepine anxiolytics produce consistent reductions in defensive threat/attack and risk assessment, while panicolytic and panicogenic drugs selectively reduce and enhance, respectively, flight. Effects of GABA A -benzodiazepine, serotonin, and neuropeptide ligands in the Mouse Defense Test Battery are reviewed. This review suggests that the Mouse Defense Test Battery is a sensitive and appropriate tool for preclinical evaluation of drugs potentially effective against defense-related disorders such as anxiety and panic. D

Section: Selective and Nonselective 5-ht-interacting Drugsmentioning

confidence: 99%

Section: Effects Of Selective and Nonselective 5-ht 2 Receptor Antagomentioning

confidence: 99%

The Mouse Defense Test Battery: pharmacological and behavioral assays for anxiety and panic

Griebel

European Journal of Pharmacology

2003

Self Cite

258

159

Neuropsychopharmacology

“…This could involve differences in 5-HT release and/or sensitivity of postsynaptic receptors, at least those that mediate citalopram indirect effects on anxiety and locomotor reactivity. In keeping with the great number of serotonergic receptors that are known to modulate anxiety-and activity-related behaviours (Griebel 1995), any suggestion as to the identity of the receptor(s) involved therein is premature.…”

Section: Do Strain-related Differences In the Behavioural Responses Tmentioning

confidence: 99%

Serotonin Reuptake Inhibition by Citalopram in Rat Strains Differing for Their Emotionality

Pollier

Sarre

Aguerre

et al. 2000

Molecular and Cellular Neuroscience

“…Since the serotonin system is involved in mediating anxiety behaviors and stress responses (Deakin 1988;Griebel, 1995;Shakesby et al, 2002), we subsequently examined whether acute stress influenced the serotonin effect on PFC neuronal excitability. The stress procedures we used entailed forcing the rat to swim in deep water for 30 min (Price et al, 2002;Roche et al, 2003).…”

Section: Nih-pa Author Manuscriptmentioning

confidence: 99%

“…has been implicated in the pathogenesis of mental disorders associated with PFC dysfunction, such as depression, anxiety and schizophrenia (Doris et al, 1999;Gross et al, 2002;Lemonde et al, 2003). The serotonin system is the major target of antidepressants, anxiolytics and atypical antipsychotics (Deakin, 1988;Griebel, 1995;Meltzer et al, 2003). …”

mentioning

confidence: 99%

Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex

Zhong

Yuen

Yan

2008

Both serotonin and NMDA signaling in prefrontal cortex (PFC) are implicated in mental disorders, including depression and anxiety. To understand their potential contributions to PFC neuronal excitability, we examined the effect of co-activation of 5-HT and NMDA receptors on action potential firing elicited by depolarizing current injection in PFC pyramidal neurons. In the presence of NMDA, a low concentration of the 5-HT 1A agonist 8-OH-DPAT substantially reduced the number of spikes, and a low concentration of the 5-HT 2A/C agonist α-Me-5HT significantly enhanced it, while both agonists were ineffective when applied alone. The 8-OH-DPAT effect on firing was mediated by inhibition of protein kinase A (PKA), whereas the α-Me-5HT effect was mediated by activation of protein kinase C (PKC). Moreover, the extracellular signal-regulated kinase (ERK), a signaling molecule downstream of PKA and PKC, was involved in both 5-HT 1A and 5-HT 2A/C modulation of neuronal excitability. Biochemical evidence showed that 5-HT 1A decreased, whereas 5-HT 2A/C increased the activation of ERK in an NMDA-dependent manner. In animals exposed to acutely stress, the enhancing effect of 5-HT 2A/C on firing was lost, while the decreasing effect of 5-HT 1A on firing was intact. Concomitantly, the effect of 5-HT 2A/C , but not 5-HT 1A , on ERK activation was abolished in stressed animals. Taken together, our results demonstrate that distinct 5-HT receptor subtypes, by interacting with NMDA receptors, differentially regulate PFC neuronal firing, and the complex effects of 5-HT receptors on excitability are selectively altered under stressful conditions, which are often associated with mental disorders.Keywords 5-HT 1A receptor; 5-HT 2 receptor; NMDA receptor; action potential firing; ERK; stress; prefrontal cortexThe prefrontal cortex (PFC) receives a dense serotonergic innervation from the raphe nuclei (Smiley and Goldman-Rakic, 1996). The serotonergic system plays an important role in regulating PFC functions, including emotional control, cognitive behaviors and working memory (Williams et al., 1996;Buhot 1997;Williams et al., 2002). Aberrant serotonin system * Correspondence should be addressed to ZhenYan, Ph.D., Department of Physiology and Biophysics, State University of New York at Buffalo, 124 Sherman Hall, Buffalo, NY, 14214, USA. Email: zhenyan@buffalo.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. This PDF receipt will only be used as the basis for generating PubMed Central (PMC) documents. PMC documents will be made available for review after conversion (approx. 2-3 weeks time)...