Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice

Lehr, E.

doi:10.1007/s00213-002-1199-7

Cited by 10 publications

(5 citation statements)

References 29 publications

(26 reference statements)

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“…Locomotion and exploratory behavior findings in the present studies are in keeping with previously published reports on pramipexole effects in other strains of mice (Lehr et al, 2002; Siuciak and Fujiwara 2004; Maj et al, 1997). 7-OH-DPAT and PD 128907, two other D3-preferential DA agonists, also reduce locomotor activity in wild-type C57BL/6J mice; this effect is not present in D3 receptor knockout mice (Pritchard et al, 2003).…”

Section: Discussionsupporting

confidence: 92%

“…Pramipexole has been found to alter nocturnal locomotion, alter operant responding (Lehr, 2002), induce hypothermia (Maj et al, 1997), and decrease the duration of immobility in the forced swim test (Kitagawa et al, 2009; Siuciak and Fujiwara, 2004). The ability to use similar PPI measures across species and the relative ease of genetic manipulations in mice makes them an attractive animal model to further study the role of D3 receptor activation in the regulation of sensorimotor gating.…”

Section: Introductionmentioning

confidence: 99%

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The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

Chang¹,

Geyer²,

Buell³

et al. 2010

Behavioural Pharmacology

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Pramipexole (PRA) is a preferential D3R agonist that in rats and humans modifies prepulse inhibition (PPI) of the acoustic startle reflex, an operational measure of sensorimotor gating. The ability to use similar PPI measures across species, and the relative ease of genetic manipulations in mice, suggests that molecular studies of the D3R regulation of sensorimotor gating might be best pursued in mice. Here, we evaluate the effects of PRA on PPI and locomotion in C57BL/6J mice, the background strain for many gene knockout mouse models. Male C57BL/6J mice were tested for PPI and locomotor activity after injection of PRA. No significant effects of PRA on PPI were seen at any dose (0.1-10.0 mg/kg), but a significant reduction in startle magnitude was observed after 10 mg/kg PRA. In contrast, the D1/2 agonist, apomorphine (5 mg/kg) significantly reduced PPI in these mice. At doses of PRA that did not alter startle magnitude (0.3, 1.0, 3.0 mg/kg), significant decreases in the amount of locomotor and investigatory behavior were observed. Distinct from findings in rats and humans, it appears that either: 1) PRA does not activate D3Rs in C57BL/6J mice, or 2) D3R agonists are not sufficient to alter PPI in this mouse strain.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

Chang¹,

Geyer²,

Buell³

et al. 2010

Behavioural Pharmacology

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“…A titration approach would not only minimize drug-related adverse effects but also allow to test the hypothesis that higher doses of pramipexole would increase, rather than decrease, reward responsiveness due to a preferential post-synaptic DA action. This speculation is consistent with (1) findings in rodents showing that pramipexole is effective in reversing anhedonia produced by the chronic mild stress paradigm (Willner et al 1994) and has antidepressant properties (Maj and Rogoz 1999;(Lehr 2002); and (2) clinical findings showing that higher doses of pramipexole ameliorate depressive symptoms in PD patients (Lemke et al 2006) and treatment-resistant depression (Corrigan et al 2000;Cassano et al 2004). Collectively, these preclinical and clinical findings raise the possibility that sustained pramipexole administration may alleviate depressive-particularly anhedonic-symptoms through its action on D3 receptors concentrated in the nucleus accumbens.…”

Section: Discussionsupporting

confidence: 89%

Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness

et al. 2007

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Rationale-The dopaminergic system, particularly D2-like dopamine receptors, has been strongly implicated in reward processing. Animal studies have emphasized the role of phasic dopamine (DA) signaling in reward-related learning, but these processes remain largely unexplored in humans.Objectives-To evaluate the effect of a single, low dose of a D2/D3 agonist-pramipexole-on reinforcement learning in healthy adults. Based on prior evidence indicating that low doses of DA agonists decrease phasic DA release through autoreceptor stimulation, we hypothesized that 0.5 mg of pramipexole would impair reward learning due to presynaptic mechanisms.Methods-Using a double-blind design, a single 0.5 mg dose of pramipexole or placebo was administered to 32 healthy volunteers, who performed a probabilistic reward task involving a differential reinforcement schedule as well as various control tasks.Results-As hypothesized, response bias toward the more frequently rewarded stimulus was impaired in the pramipexole group, even after adjusting for transient adverse effects. In addition, the pramipexole group showed reaction time and motor speed slowing and increased negative affect; however, when adverse physical side effects were considered, group differences in motor speed and negative affect disappeared.Conclusions-These findings show that a single low dose of pramipexole impaired the acquisition of reward-related behavior in healthy participants, and they are consistent with prior evidence suggesting that phasic DA signaling is required to reinforce actions leading to reward. The potential implications of the present findings to psychiatric conditions, including depression and impulse control disorders related to addiction, are discussed.

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“…In line with the above observations, agonists at closely related D 2 , D 3 , and D 4 receptors, such as the antiparkinsonian agents ropinirole, pramipexole, and bromocriptine, are active in experimental models of potential antidepressant activity (Willner, 1995;Lehr, 2002). In clinical trials in Parkinson and non-Parkinson patients, D 2 /D 3 receptor agonists have also shown antidepressant properties, both alone and in synergy with selective serotonin (5-HT) reuptake inhibitors (Weddell and Weiser, 1995;Corrigan et al, 2000).…”

mentioning

confidence: 68%

S32504, a Novel Naphtoxazine Agonist at Dopamine D₃/D₂ Receptors: III. Actions in Models of Potential Antidepressive and Anxiolytic Activity in Comparison with Ropinirole

Millan¹,

Brocco²,

Papp³

et al. 2004

J Pharmacol Exp Ther

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In forced-swim tests in mice and rats, the novel D 3 /D 2 receptor agonist S32504 [(ϩ)-trans-3,4,4a,5,6,10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth[1,2-b]-1,4-oxazine] dose-dependently (0.04 -2.5 mg/kg) and stereospecifically suppressed immobility compared with its enantiomer S32601 [(Ϫ)-trans-3,4,4a,5,6,10b-hexahydro-9-carbamoyl-4-propyl-2H-naphth-[1,2-b]-1,4-oxazine]. Ropinirole was less potent than S32504 in this procedure, and it was likewise less potent than S32504 (0.04 -2.5 mg/kg) in attenuating motor-suppressant properties of the ␣ 2 -adrenoceptor agonist S18616 [(S)-spiro[(1-oxa-2-amino-3-azacyclopent-2-ene)-4,2Ј-(1Ј,2Ј,3Ј,4Ј-tetrahydronaphthalene)]]. In a learned helplessness paradigm, S32504 (0.08 -2.5 mg/kg) suppressed escape failures. Furthermore, in a chronic mild stress model of anhedonia, S32504 (0.16 -2.5 mg/kg) rapidly restored the suppression of sucrose consumption. S32504 inhibited marble-burying behavior in mice (0.04 -0.16 mg/kg) and aggressive behavior in isolated mice (0.04 -2.5 mg/kg): only higher doses of ropinirole mimicked these actions of S32504. In tests of anxiolytic activity, S32504 was more potent (0.0025-0.16 mg/kg) than ropinirole in suppressing fear-induced ultrasonic vocalizations, and S32601 was inactive. Furthermore, in contrast to ropinirole, S32504 modestly enhanced punished responses in a Vogel conflict procedure and increased open-arm entries in a plus-maze. At doses active in the above-described procedures, S32504 did not elicit hyperlocomotion. In the forced-swim, marble-burying, and ultrasonic vocalization models, actions of S32504 were Although the most familiar feature of Parkinson's disease is a disruption of motor function, it is accompanied by mood, sensory, and cognitive symptoms (Giladi et al., 2000). These often anticipate onset of frank motor dysfunction and are, in general, poorly treated by the prototypical antiparkinsonian agent L-3,4-dihydroxyphenylalanine (Giladi et al., 2000;Rascol et al., 2003). A perturbation of adrenergic, serotonergic, and cholinergic transmission likely contributes to these interrelated features of Parkinson's disease, but the principal underlying deficit is a degeneration of nigrostriatal dopaminergic projections together with a (less pronounced) dysfunction of mesolimbic and mesocortical dopaminergic pathways (Rascol et al., 2003). Interestingly, as indicated by the following observations, a disruption of dopaminergic transmission is implicated in the depressed mood displayed both by ParArticle, publication date, and citation information can be found at

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Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice

Abstract: Based on other preclinical data and initial clinical results, we speculate that these effects may reflect anti-anhedonic/antidepressive properties of pramipexole.

Cited by 10 publications

References 29 publications

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness

S32504, a Novel Naphtoxazine Agonist at Dopamine D₃/D₂ Receptors: III. Actions in Models of Potential Antidepressive and Anxiolytic Activity in Comparison with Ropinirole

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Potential antidepressant properties of pramipexole detected in locomotor and operant behavioral investigations in mice

Abstract: Based on other preclinical data and initial clinical results, we speculate that these effects may reflect anti-anhedonic/antidepressive properties of pramipexole.

Cited by 10 publications

References 29 publications

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

The effects of pramipexole on prepulse inhibition and locomotor activity in C57BL/6J mice

Single dose of a dopamine agonist impairs reinforcement learning in humans: Behavioral evidence from a laboratory-based measure of reward responsiveness

S32504, a Novel Naphtoxazine Agonist at Dopamine D3/D2 Receptors: III. Actions in Models of Potential Antidepressive and Anxiolytic Activity in Comparison with Ropinirole

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S32504, a Novel Naphtoxazine Agonist at Dopamine D₃/D₂ Receptors: III. Actions in Models of Potential Antidepressive and Anxiolytic Activity in Comparison with Ropinirole