From: Animal models for bipolar disorder: from bedside to the cage
Manipulation | BD-relevant behavior | Neurobiology | References |
---|---|---|---|
Circadian rhythm | |||
ClockΔ19 mutant mice | Hyperactivity | Altered sleep pattern | (Coque et al. 2011; van Enkhuizen et al. 2013b; McClung 2013; McClung et al. 2005; Mukherjee et al. 2010; Roybal et al. 2007) |
Altered sleep pattern | Enhanced DA release | ||
Greater preference for rewarding stimuli | |||
Decreased anxiety behavior | |||
Less depressive-like behavior | |||
Impaired PPI | |||
CLOCK knock-down mice | Abnormal circadian rhythms | ||
Less anxiety | |||
Hyperactivity in novel environment but decreased overall hyperactivity | |||
Increased depression-like behavior and helplessness | |||
GSK-3β haploinsufficient mutant mice | Reduced exploration | Affect gene transcription, neurogenesis, and apoptosis | (Besing et al. 2015; O’Brien et al. 2004, 2011; Prickaerts et al. 2006) |
Less helplessness | |||
Normal overall activity | |||
GSK-3β over-expression mice | Hyperactivity | Alterations of dopaminergic system | |
Less helplessness | |||
Reduced habituation | |||
Increased acoustic startle response | |||
ERK1 knock-out mice | Hyperactivity | Shift of activity rhythm | (Engel et al. 2008) |
Enhanced goal-directed activity | |||
Increased risk taking and impulsivity | |||
Increased reward seeking | |||
BDNF haploinsufficient mutant mice | Hyperactivity | Decreased BDNF level following DA overactivity | (Kernie et al. 2000; Lyons et al. 1999; Magariños et al. 2011) |
Increased aggression | |||
Elevated appetite | Decreased hippocampal volume | ||
CA3 dendritic arborizations resemble stressed wild-type mice | |||
Bcl-2 heterozygous knock-out mice | Increased anxiety | Decreased Bcl-2 level | (DeVries et al. 2001; Einat et al. 2005; Lien et al. 2008; Rondi-Reig et al. 1997; Rondi-Reig and Mariani 2002) |
Increased reward seeking | |||
Acts protective against deleterious stress-induced neuronal endangerment | |||
Increased amphetamine sensitization | |||
DBP heterozygotous knock-out mice | Hypoactivity | (Le-Niculescu et al. 2008) | |
Diminished response to amphetamine | |||
Environmental stress induce hyperactivity | |||
Sleep deprivation | Hyperactivity | (Benedetti et al. 2008; Gessa et al. 1995; Hicks et al. 1979; Malkoff-Schwartz et al. 1998; Morden et al. 1968) | |
Increased aggression | |||
Increased exploratory behavior | |||
Hypersexuality | |||
High-frequency stimulation of the lateral hypothalamus | Hyperactivity | Affects sleep–wake cycle | |
Increased grooming | |||
Hypersexuality | |||
Reduced resting phases | |||
Photoperiod lengths | Anxiety behavior | Neurotransmitter switching | (Dulcis et al. 2013) |
Helplessness | |||
(DA ↔ somatostatin) | |||
Sensitization models | |||
Administration of psychostimulants (amphetamine, cocaine) | Hyperactivity | Increased synaptic DA and NE levels | (Borison et al. 1978; Davies et al. 1974; Frey et al. 2006; Fries et al. 2015; Gould et al. 2001; Kilbey and Ellinwood 1977; Macêdo et al. 2012, 2013; Post 1992; Post 1990; Queiroz et al. 2015; Rezin et al. 2014; Rygula et al. 2015; Seiden et al. 1993; Zheng et al. 2013) |
Increased aggression | |||
Disturbance of homeostatic mechanisms | |||
Stereotypies | |||
Increased hedonic behavior | |||
Alterations in BDNF level | |||
Disturbed sleep–wake cycle | |||
Declined cognitive performance | |||
Deficient PPI response | |||
Withdrawal following chronically psychostimulant administration | Hypoactivation | Supersensitivity of serotoninergic neurons a decrease in NE | (Barr et al. 1999; Barr and Phillips 1999, 2002; Baumann and Rothman 1998; Markou and Koob 1991; Marszalek-Grabska et al. 2016; Mutschler and Miczek 1998; Paulson et al. 1991; Schindler et al. 1994; Schwartz et al. 1982; Wise and Munn 1995) |
Increased anxiety | |||
Anhedonia | |||
Increased negative contrast | |||
Reduced DA responsiveness | |||
Decreased motivation | |||
Dopaminergic pathways | |||
Increased D1R expression in the prefrontal cortex | Increased impulsivity | Decreased D2R in nucleus accumbens | |
Increased sexual behavior | |||
Hedonic behavior | |||
Addictive behavior | |||
Termination of previous D1R over-expression | Hypoactivity | Increased CREB in nucleus accumbens | (Freund et al. 2016) |
Anhedonic behavior | |||
Helplessness | |||
DAT knock-down mice | Hyperactivity in novel environments | Hyperdopaminergia | (Dulcis et al. 2013; van Enkhuizen et al. 2014b; van Enkhuizen et al. 2014a; Giros et al. 1996; Ralph et al. 2001; Ralph-Williams et al. 2003; Young et al. 2010, 2011; Zhuang et al. 2001) |
Increased risk behavior | |||
Hyperexploratory behavior | |||
Less anxiety | |||
Impaired decision making with a preference for high reward combined with high risk | |||
DAT knock-out mice | Hyperactivity | ||
Sensorimotor deficits within PPI | |||
GluR6 knock-out mice | Hyperactivity | (Shaltiel et al. 2008) | |
Increased risk taking | |||
Elevated aggression | |||
Heightened responsivity to amphetamine | |||
Less anxiety | |||
Environmental stressors | |||
Prenatal stress | Hyperactivity in novel environment | Incomplete development of hippocampus and reduced weight of the prefrontal cortex and nucleus accumbens | (Clarke and Schneider 1993; Coe et al. 2003; Diz-Chaves et al. 2012; Fatima et al. 2017; Frye and Wawrzycki 2003; Guan et al. 2013; Hao et al. 2010; Jia et al. 2015; Koehl et al. 1999; Lemaire et al. 2000; Lin et al. 2012; Lin and Wang 2014; Uno et al. 1990; Wakshlak and Weinstock 1990) |
Hypersensitivity to amphetamine | |||
Anhedonia | |||
Increased helplessness | |||
Alterations in HPA axis and neurotransmitter levels in early development | |||
Increased anxiety | |||
Impaired cognition including working memory deficits | |||
Reduced BDNF levels | |||
Decreased exploratory behavior | Decreased Bcl-2 level | ||
Diminished neurogenesis | |||
Increased mGluR1 and mGluR2 | |||
Altered immune system | |||
Stimulating dopaminergic transmission | |||
Social withdrawal | |||
Postnatal stress | Hypoactivity | Hippocampal development, memory, spatial and social learning, response to stress of the HPA axis | (Caldji et al. 2000b; Duman et al. 2016; Duman and Monteggia 2006; Huot et al. 2002; Huot et al. 2001; Kalinichev et al. 2002; Ladd et al. 2000, 2004; Lippmann et al. 2007; Magariños et al. 2011; McIntosh et al. 1999; Wigger and Neumann 1999) |
Increased stereotypies | |||
Increased anxiety behavior | |||
Heightened response to acute stressor | |||
Decreased BDNF level | |||
Elevated PPI response | |||
Neuronal atrophy | |||
Stimulating dopaminergic transmission | |||
Chronic stress (through, e.g., repeated social defeat) | Depressive-like behavior | Disrupted circadian rhythms and immune function | (Berton et al. 1998; Crawford et al. 2013; Hollis et al. 2010; Hollis and Kabbaj 2014; Leuner et al. 2014; Maier and Seligman 1976; Meerlo et al. 1996; Porsolt et al. 1977; Ruis et al. 1999; Steru et al. 1985; Tidey and Miczek 1997; Tornatzky and Miczek 1993; Wulsin et al. 2016) |
Hypoactivity | |||
Reduced exploration | |||
Reduced aggression | |||
Hyposexuality | |||
Elevated anxiety | |||
Submissive behavior | |||
Social avoidance | |||
Immune system | |||
Maternal immune activation | Increased locomotor response to amphetamine | Increased inflammation | (Bakos et al. 2004; Cotter et al. 1995; Eßlinger et al. 2016; Fernández de Cossío et al. 2017; Kneeland and Fatemi 2013; Meyer et al. 2005; Remus and Dantzer 2016; Ronovsky et al. 2017; Rose et al. 2017; Shi et al. 2003; Wachholz et al. 2017; Zuckerman et al. 2003) |
Increased striatal DA release | |||
Increased repetitive and stereotypic behavior | |||
Increased anxiety | |||
Helplessness | |||
Disrupted sensorimotor gating | |||
Impaired working memory |