Effect of GBR12909 on affective behavior: Distinguishing motivational behavior from antidepressant-like and addiction-like behavior using the runway model of intracranial self-stimulation

Esumi, Satoru; Sagara, Hidenori; Nakamoto, Akihiko; Kawasaki, Yoichi; Gomita, Yutaka; Sendo, Toshiaki

doi:10.1016/j.bbr.2012.10.051

Cited by 12 publications

(5 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, we reported that chronic valproate at human therapeutic blood levels for BD attenuated the mania-like pattern induced by GBR12909 (van Enkhuizen et al 2013a). Moreover, GBR12909 increased measures of motivation (van Enkhuizen et al 2013b) and sped responding in mice (Young and Geyer 2010), while low doses (5 mg/kg) also reduced immobility time in the FST (Esumi et al 2013) and impaired PPI (Kwek and van den Buuse 2013), consistent with reported PPI deficits in patients with BD mania (Perry et al 2001). Increasing DA functional activity by inhibiting the DAT thus results in different facets of behavior in rodents relevant to mania in humans.…”

Section: Discussionsupporting

confidence: 73%

“…Both DAT knockdown (KD) mice and mice receiving the selective DAT inhibitor GBR12909 exhibit hyperactivity, increased exploration, and straight paths of movement as quantified by the mouse behavioral pattern monitor (BPM) (Young et al 2010a; b) similar to patients with BD mania (Minassian et al 2011; Perry et al 2010) and euthymia (Henry et al 2013) in a human BPM. Although some of the abnormal behavior observed in these GBR12909-treated mice, such as impaired decision-making (van Enkhuizen et al 2013b), is also present in depressed patients with BD performing similar human tasks (Adida et al 2011), their hyperactivity, increased motivation (Young and Geyer 2010), and reduced immobility times in the tail suspension test (TST) (Sarkisyan et al 2010) and FST (Esumi et al 2013) more closely model the manic phase of BD. Furthermore, dysfunctional sensorimotor gating of the startle reflex as measured by reduced prepulse inhibition (PPI) has been observed in manic patients with BD (Perry et al 2001), but not in depressed subjects (Perry et al 2004; Quednow et al 2006), suggesting that dysfunctional PPI is state dependent (Kohl et al 2013).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features

et al. 2015

View full text Add to dashboard Cite

Rationale Bipolar disorder (BD) is a disabling and life-threatening disease characterized by states of depression and mania. New and efficacious treatments have not been forthcoming partly due to a lack of well-validated models representing both facets of BD. Objectives We hypothesized that cholinergic- and dopaminergic-pharmacological manipulations would model depression and mania respectively, each attenuated by lithium treatment. Methods C57BL/6J mice received the acetylcholinesterase inhibitor physostigmine or saline before testing for ‘behavioral despair’ (immobility) in the tail-suspension test (TST) and forced-swim test (FST). Physostigmine effects on exploration and sensorimotor gating were assessed using the cross-species behavioral pattern monitor (BPM) and prepulse inhibition (PPI) paradigms. Other C57BL/6J mice received chronic lithium drinking water (300, 600, or 1200 mg/l) before assessing their effects alone in the BPM or with physostigmine on FST performance. Another group was tested with acute GBR12909 (dopamine transporter inhibitor) and chronic lithium (1000 mg/l) in the BPM. Results Physostigmine (0.03 mg/kg) increased immobility in the TST and FST without affecting activity, exploration, or PPI. Lithium (600 mg/l) resulted in low therapeutic serum concentrations and normalized the physostigmine-increased immobility in the FST. GBR12909 induced mania-like behavior in the BPM of which hyper-exploration was attenuated, though not reversed, after chronic lithium (1000 mg/ml). Conclusions Increased cholinergic levels induced depression-like behavior and hyperdopaminergia induced mania-like behavior in mice, while chronic lithium treated some, but not all, facets of these effects. These data support a cholinergic-monoaminergic mechanism for modeling BD aspects and provide a way to assess novel therapeutics.

show abstract

Section: Discussionsupporting

confidence: 73%

Section: Introductionmentioning

confidence: 99%

Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Demyttenaere et al (2005) suggested that the neurological basis of motivational symptoms such as fatigue is governed by specific neural circuits, therefore the specific symptom profiles of depression need to be evaluated in the context of the drug and its neurobiological mechanism of action (see also Cooper et al, 2014). The present studies, in combination with additional clinical and preclinical reports Correa 2002, 2012;Salamone et al, 2003Salamone et al, , 2007Treadway et al, 2011;Mai et al, 2012;Esumi et al, 2013;Pizzagali 2014), indicate that compared to other monoamines, DA appears to be a key component of the specific circuitry regulating effortrelated motivational dysfunctions.…”

Section: Discussionmentioning

confidence: 79%

“…The doses of fluoxetine and desipramine were based on studies involving traditional rodent antidepressant screening tests (Armario et al, 1988;Jang et al, 2009), and recent studies showing that fluoxetine suppresses locomotion and induces tremor in TBZ-treated rats . The doses of GBR were based upon rodent runway studies (Esumi et al, 2013).…”

Section: Pharmacological Agents and Dose Selectionmentioning

confidence: 99%

Not All Antidepressants Are Created Equal: Differential Effects of Monoamine Uptake Inhibitors on Effort-Related Choice Behavior

Yohn

Collins

Contreras-Mora

et al. 2015

Neuropsychopharmacol

View full text Add to dashboard Cite

Motivated behavior can be characterized by behavioral activation and high work output. Moreover, people with depression and other disorders show effort-related motivational symptoms, such as anergia, psychomotor retardation, and fatigue. Effort-based decision making is studied using tasks offering choices between high effort options leading to highly valued reinforcers vs low effort/low reward options, and such tasks could be useful as animal models of motivational symptoms. In the present studies the effort-related effects of the vesicular monoamine transport (VMAT-2) inhibitor tetrabenazine (TBZ) were investigated. TBZ blocks vesicular storage and also produces depressive symptoms in humans. Moreover, TBZ alters effort-based choice in rats, biasing animals toward low effort alternatives. The present studies investigated the ability of acute administration of various monoamine uptake inhibitors to reverse the effects of TBZ. Effort-related effects of TBZ were attenuated by the catecholamine uptake inhibitor and antidepressant bupropion, and this effect of bupropion was reversed by either D1 or D2 family antagonism. The effort-related effects of TBZ were also attenuated by the selective dopamine uptake blocker GBR12909. The 5-HT uptake inhibitor fluoxetine and the norepinephrine uptake inhibitor desipramine failed to reverse the effects of TBZ, and higher doses of these drugs, given alone or in combination with TBZ, led to further behavioral impairments. These results indicate that drugs acting on dopamine transmission are relatively effective at reversing the effort-related effects of TBZ, and are consistent with the hypothesis that drugs that enhance dopamine transmission may be effective at treating effort-related psychiatric symptoms in humans.

show abstract

“…However, in the case of vanoxerine (DARI) the result was opposite to that expected from studies on laboratory rodents. As vanoxerine rapidly increases the level of dopamine 30 min after injection, it usually increases physical activity in rats (e.g., Esumi et al. 2013).…”

Section: Discussionmentioning

confidence: 99%

The effect of monoamines reuptake inhibitors on aerobic exercise performance in bank voles from a selection experiment

Jaromin¹,

Sadowska²,

Koteja³

2018

Current Zoology

View full text Add to dashboard Cite

Exercise performance depends on both physiological abilities (e.g., muscle strength) and behavioral characteristics (e.g., motivation). We tested the hypothesis that evolution of increased aerobic exercise performance can be facilitated by evolution of neuropsychological mechanisms responsible for motivation to undertake physical activity. We used a unique model system: lines of bank voles Myodes glareolus selected for high swim-induced aerobic metabolism ("aerobic" A lines). In generation 21, voles from the 4 A lines achieved a 57% higher "voluntary maximum" swiminduced aerobic metabolism (VO 2 swim) than voles from 4 unselected, "control" C lines. In C lines, VO 2 swim was 9% lower than the maximum forced-exercise aerobic metabolism (VO 2 run; P ¼ 0.007), while in A lines it was even higher than VO 2 run, although not significantly (4%, P ¼ 0.15). Thus, we hypothesized that selection changed both the aerobic capacity and the neuronal mechanisms behind motivation to undertake activity. We investigated the influence of reuptake inhibitors of dopamine (DARI), serotonin (SSRI), and norepinephrine (NERI) on VO 2 swim. The drugs decreased VO 2 swim both in C and A lines (% decrease compared with saline: DARI 8%, P < 0.001; SSRI 6%, P < 0.001; NERI 8%, P < 0.001), but the proportional response differed between selection directions only for NERI (stronger effect in C lines: P ¼ 0.008) and the difference was marginally non-significant for SSRI (P ¼ 0.07) and DARI (P ¼ 0.06). Thus, the results suggest that all the 3 monoamines are involved in signaling pathways controlling the motivation to be active and that norepinephrine could have played a role in the evolution of increased aerobic exercise performance in our animal model.

show abstract

Effect of GBR12909 on affective behavior: Distinguishing motivational behavior from antidepressant-like and addiction-like behavior using the runway model of intracranial self-stimulation

Cited by 12 publications

References 42 publications

Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features

Modeling bipolar disorder in mice by increasing acetylcholine or dopamine: chronic lithium treats most, but not all features

Not All Antidepressants Are Created Equal: Differential Effects of Monoamine Uptake Inhibitors on Effort-Related Choice Behavior

The effect of monoamines reuptake inhibitors on aerobic exercise performance in bank voles from a selection experiment

Contact Info

Product

Resources

About