Biphasic effect of D-2 agonist quinpirole on locomotion and movements

Eilam, David; Szechtman, Henry

doi:10.1016/0014-2999(89)90837-6

Cited by 232 publications

(128 citation statements)

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“…Rather, our aim was to reveal potential alterations in the D2 receptors of this obese strain at either the pre-, or the postsynaptic domain, or both. Our findings are in concert with earlier reports showing that behavioral responses to acute peripheral quinpirole injection are biphasic, time and dose dependent [20]. Low dose of quinpirole (< 0.1 mg/kg) induces behavioral inhibition, while higher doses elicit a biphasic response; brief decrease in behavioral activity followed by a period of hyperactivity.…”

Section: Differential Strain Effects Of D2 Agonist On Activitysupporting

confidence: 91%

“…Low dose of quinpirole (< 0.1 mg/kg) induces behavioral inhibition, while higher doses elicit a biphasic response; brief decrease in behavioral activity followed by a period of hyperactivity. A low dose of quinpirole can act preferably on DA D2 presynaptic receptors, which inhibits DA release, while higher dose activates both pre-and postsynaptic receptors, eliciting increased response of postsynaptic DA receptors [15,20,47]. On the other hand, a more pronounced inhibition on OLETF rats' activity by low-dose of quinpirole is likely to be a result of increased response of presynaptic D2R receptors.…”

Section: Differential Strain Effects Of D2 Agonist On Activitymentioning

confidence: 99%

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Altered dopamine D2 receptor function and binding in obese OLETF rat

Hajnal

Margas

Covașă

2008

Brain Research Bulletin

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A decrease in D2 -like receptor (D2R) binding in the striatum has been reported in obese individuals and drug addicts. Although natural and drug rewards share neural substrates, it is not clear whether such effects contribute also to overeating on palatable meals as an antecedent of dietary obesity. Therefore, we investigated receptor density and the effect of the D2R agonist quinpirole (0.05, 0.5 mg/kg, S.C.) on locomotor activity and sucrose intake in a rat model of diet-induced obesity, the CCK-1 receptor-deficient Otsuka Long Evans Tokushima Fatty (OLETF) rat. Compared to agematched lean controls (LETO), OLETF rats expressed significantly lower [125I]-iodosulpride binding in the accumbens shell (−16%, p<0.02). Whereas the high dose of quinpirole increased motor activity in both strains equally, the low dose reduced activity more in OLETF. Both doses significantly reduced sucrose intake in OLETF but not LETO. These findings demonstrate an altered D2R signaling in obese OLETF rats similar to drug-induced sensitization and suggest a link between this effect and avidity for sucrose in this model.

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Section: Differential Strain Effects Of D2 Agonist On Activitysupporting

confidence: 91%

Section: Differential Strain Effects Of D2 Agonist On Activitymentioning

confidence: 99%

Altered dopamine D2 receptor function and binding in obese OLETF rat

Hajnal

Margas

Covașă

2008

Brain Research Bulletin

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“…These effects can be described within a framework identified previously (Eilam and Szechtman, 1989;Szechtman et al, 1994a, b) for the time course of the locomotor response to acute and chronic QNP, a framework also evident in the present study for the QNP alone rats (Figure 2, VQhigh group). Typically, the locomotor response to acute QNP has three phases: a period of initial inhibition lasting about 5 min, a second phase of relative inhibition for an additional 15-30 min, followed finally by a period of locomotor excitation, compared to saline controls.…”

Section: Effect Of U69593 On Development Of Sensitization To Qnpsupporting

confidence: 78%

“…Again, such an inference follows from the uncoupling of changes produced by kappa agonist coadministration. Normally, there are two phases to the depressive effects of QNP during the course of drug action: an initial inhibitory period that lasts about 5 min and a subsequent relative inhibitory phase that lasts from 5 to 20 min after drug injection, with only the relative inhibitory phase gradually diminishing across injections and ultimately becoming supplanted by locomotor excitation (Eilam and Szechtman, 1989;Szechtman et al, 1994a, b;present study). However, chronic cotreatment of U69593 with the presynaptic dose of QNP resulted in tolerance of the initial inhibition, an effect that was not observed during cotreatment of U69593 with a postsynaptic dose of QNP.…”

Section: Components Of Sensitizationmentioning

confidence: 49%

“…Second, neurochemical studies show that similarly low doses of dopamine agonists, including QNP, are effective in the inhibition of dopamine release mediated by D2-like presynaptic receptors (Acri et al, 2001;Imperato et al, 1988;Shilliam and Heidbreder, 2003). Finally, behavioral studies show that similarly low doses of dopamine agonists, including QNP, induce locomotor hypoactivity, but doses of QNP greater than 0.1 mg/kg induce locomotor excitation (Dall'Olio et al, 2002;Eilam et al, 1992;Eilam and Szechtman, 1989;King et al, 1999;Szechtman et al, 1994a;Van Hartesveldt et al, 1992). That the inhibitory effect of low dose QNP on locomotion is produced by stimulation of dopamine autoreceptors is supported by the finding that such doses are inhibitory in the D2Long knockout mice, but not in D2 receptor null mice (Usiello et al, 2000;Wang et al, 2000).…”

Section: Drugsmentioning

confidence: 99%

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Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

Perreault

Graham

Bisnaire

et al. 2005

Neuropsychopharmacol

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To assess whether the development and expression of behavioral sensitization to the dopamine D2/D3 agonist quinpirole (QNP) is influenced by coadministration of the kappa opioid receptor agonist U69593, rats received every 3-4 days for a total of 10 treatments an injection of U69593 (0.3 mg/kg) together with an injection of either a postsynaptic (0.5 mg/kg) or a presynaptic dose of QNP (0.05 mg/ kg); locomotor activity was measured after each treatment. Control rats were injected as appropriate with QNP, U69593, and vehicle/ saline. Following chronic treatment, dose-response profiles to QNP were obtained to assess the expression of sensitization; the effect of U69593 on locomotor activity in animals already sensitized to QNP was also assessed. Results showed that cotreatment of U69593 with a postsynaptic dose of QNP doubled the speed and magnitude of sensitization to QNP, while U69593 cotreatment with a presynaptic dose of QNP switched the effects of QNP from locomotor depression to locomotor sensitization. However, U69593 cotreatment with a presynaptic dose of QNP changed a different set of measures of sensitization than did cotreatment with a postsynaptic dose of the dopamine agonist. Together, findings suggest that sensitization to QNP is not a unitary phenomenon but has components that are relatively independent, mediated by distinct pre-and postsynaptic mechanisms and modulated by kappa receptor activity.

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DAD1- and DAD2-like agonist effects on motor activity of C57 mice: Differences compared to rats

Halberda

Middaugh

Gard

et al. 1997

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Studies on rats indicate that DAD1- and DAD2-like agonists produce a biphasic action on motor activity, with low doses reducing activity below control levels, and higher doses initially reducing, then elevating, activity for a prolonged period. Although some of the reported effects of DAD1- and DAD2-like receptor agonists on motor activity of mice are consistent with their effects on rats, the possibility of species differences is also apparent. In the current study the effects of DAD1- and DAD2-like agonists on motor activity of C57BL/6 (C57) mice were determined to establish species consistencies and differences with respect to their effects on rats. The partial DAD1-like agonist SKF 38393 reduced the activity of C57 mice at low doses and elevated activity above control levels at higher doses, if the mice were thoroughly habituated to the test chamber. The full DAD1 agonist SKF 82958 also increased the activity of C57 mice, and along with the SKF 38393 results indicates a response to DAD1 receptor stimulation similar to that reported for rats. In contrast to the species similarity in response to DAD1 stimulation, the DAD2-like agonist quinpirole produced only a dose-responsive monotonic reduction in the activity of C57 mice, whether the animals were nonhabituated or well-habituated to the testing environment, male or female, young or mid-aged, injected intraperitoneally (i.p.) or subcutaneously (s.c.), and with either low or high doses. This apparent species difference in response to quinpirole might reflect distinguishable functional properties of the DA subreceptor systems.

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Biphasic effect of D-2 agonist quinpirole on locomotion and movements

Cited by 232 publications

References 19 publications

Altered dopamine D2 receptor function and binding in obese OLETF rat

Altered dopamine D2 receptor function and binding in obese OLETF rat

Kappa-Opioid Agonist U69593 Potentiates Locomotor Sensitization to the D2/D3 Agonist Quinpirole: Pre- and Postsynaptic Mechanisms

DAD1- and DAD2-like agonist effects on motor activity of C57 mice: Differences compared to rats

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