Estrogen deficient male mice develop compulsive behavior.
ABSTRACT Aromatase converts androgen to estrogen. Thus, the aromatase knockout (ArKO) mouse is estrogen deficient. We investigated the compulsive behaviors of these animals and the protein levels of catechol-O-methyltransferase (COMT) in frontal cortex, hypothalamus and liver.
Grooming was analyzed during the 20-min period immediately following a water-mist spray. Running wheel activity over two consecutive nights and barbering were analyzed. COMT protein levels were measured by Western analysis.
Six-month old male but not female ArKO mice develop compulsive behaviors such as excessive barbering, grooming and wheel-running. Excessive activities were reversed by 3 weeks of 17beta-estradiol replacement. Interestingly, the presentation of compulsive behaviors is accompanied by concomitant decreases (p < .05) in hypothalamic COMT protein levels in male ArKO mice. These values returned to normal upon 17beta-estradiol treatment. In contrast, hepatic and frontal cortex COMT levels were not affected by the estrogen status, indicating region- and tissue-specific regulation of COMT levels by estrogen. No differences in COMT levels were detectable between female animals of both genotypes.
This study describes the novel observation of a possible link between estrogen, COMT and development of compulsive behaviors in male animals which may have therapeutic implications in obsessive compulsive disorder (OCD) patients.
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ABSTRACT: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric condition estimated to afflict 1-3% of the world population. The estimated financial impact in the treatment and management of OCD is in the billions of dollars annually in the US alone. At present there is a marked lack of evidence on the specific causes of OCD. Current hypotheses largely focus on the serotonin (5-HT) system on the basis of the effectiveness of selective serotonin reuptake inhibitors (SSRIs) in alleviating symptoms of patients with OCD, yet a considerable fraction of patients are non-responsive or minimally responsive to these agents. Despite this fact, SSRIs have remained the primary pharmacological treatment avenue for OCD. In recent years, multiple lines of evidence have implicated glutamatergic synaptic dysfunction within the cortico-striatal-thalamo-cortical (CSTC) brain circuit in the etiology of OCD and related disorders, thereby prompting intensified effort in the development and evaluation of agents that modulate glutamatergic neurotransmission for the treatment of OCD. With this in mind, here we review the following topics with respect to synaptic dysfunction and the neural circuitry underlying OCD: (1) evidence supporting the critical involvement of the CSTC circuit, (2) genetic studies supporting the involvement of glutamatergic dysfunction, (3) insights from genetic animal models of OCD, and (4) preliminary findings with glutamatergic neurotransmission-modulating agents in the treatment of OCD. Given the putative mechanistic overlap between OCD and the broader OC-spectrum of disorders, unraveling the synaptic basis of OCD has potential to translate into more effective treatments for an array of poorly understood human disorders.Current Chemical Genomics 01/2008; 2:62-75.
Chapter: Analysis of Grooming Behavior and Its Utility in Studying Animal Stress, Anxiety, and Depression[show abstract] [hide abstract]
ABSTRACT: In rodents, grooming is a complex and ethologically rich behavior, sensitive to stress and various genetic and pharmacological manipulations, all of which may alter its gross activity and patterning. Observational analysis of grooming activity and its microstructure may serve as a useful measure of stress and anxiety in both wild and laboratory animals. Few studies have looked at grooming behavior more than cursorily, though in-depth analysis of the behavior would immensely benefit fields utilizing rodent research. Here, we present a qualitative approach to grooming activity and patterning analysis in mice, which provides insight into the effects of stress, anxiety, and depression on this behavioral domain. The method involves quantification of the transitions between different stages of grooming, the percentages of incorrect or incomplete grooming bouts, as well as the regional distribution of grooming activity. Using grooming patterning as a behavioral endpoint, this approach permits assessment of stress levels of individual animals, allows identification of grooming phenotypes in various mouse strains, and has vast implications in biological psychiatry, including psychopharmacology, genetics, neurophysiology, and experimental modeling of affective disorders. Key wordsGrooming behavior–stress–anxiety–depression–behavioral organization (sequencing)–animal experimental and genetic models–neuropsychiatric disorders03/2009: pages 21-36;
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ABSTRACT: Obsessive-compulsive disorder (OCD) inflicts uncontrollable, intrusive thoughts and ritualistic, compulsive behaviors affecting approximately 3% of the population. Clinical symptoms of OCD can be categorized as checking, hoarding, washing, or ordering. Mounting evidence suggests that OCD phenotypes can be modeled effectively, and with remarkable validity, through translational approaches in ethological animal models. Experimental models of OCD-like behavior, including nesting, marble burying, grooming, spatial alternation, and barbering allow researchers to investigate the neurobiological mechanisms responsible for this disorder. While its exact pathogenesis remains unknown, genetic factors also play a key role in OCD. Genetic animal models of OCD and related disorders are now becoming available, aiding researchers in identifying associated neural pathways and pharmacological treatments. Here, we discuss how some genetically modified animals may be used for modeling OCD-like endophenotypes. Key wordsObsessive-compulsive disorder-Genetic animal models-Behavioral perseverations12/2009: pages 139-149;