Locomotor sensitization to quinpirole: environment-modulated increase in efficacy and context-dependent increase in potency

Szumlinski, Karen K.; Allan, Melissa; Talangbayan, Hazel; Tracey, Alison; Szechtman, Henry

doi:10.1007/s002130050442

Cited by 64 publications

(47 citation statements)

References 48 publications

(57 reference statements)

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“…The one exception was in the group of rats sensitized by cotreatment of U69593 with 0.5 mg/kg of QNP (Figure 5a, right panel). A similar difference between the response to 1 and 0.2 mg/kg of QNP had been observed in other studies (Szumlinski et al, 1997(Szumlinski et al, , 2000 but not always (Lomanowska et al, 2004). We do not have an explanation for this drop in the dose-response curve, as mouthing is not necessarily a feature of the higher dose of QNP.…”

Section: Effect Of U69593 On Expression Of Sensitization To Qnpsupporting

confidence: 88%

“…For development of sensitization, I 50 and R max are taken as measures of the speed of sensitization and the maximum capacity attained, respectively; for expression of sensitization, ED 50 and R max are taken as indices of the drug's potency and efficacy, respectively. The use of this function for sensitization to QNP was described previously (Szechtman et al, 1994b;Szumlinski et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

“…These doses were selected so as to sample the sensitized dose-response curve described previously (Lomanowska et al, 2004;Szumlinski et al, 1997), taking into account its steep slope in the dose range from 0.04 to 0.08 mg/kg of QNP.…”

Section: Drugsmentioning

confidence: 99%

“…It had been proposed that the depressive effects of dopamine agonists probably reflect stimulation of presynaptic dopamine receptors (Clark et al, 1985;Richtand et al, 2001;Starr and Starr, 1986). During the course of repeated administrations, the depressive effects of dopaminomimetic drugs diminish and the excitatory locomotor responses become stronger, occur sooner, and to lower doses of the drug (Segal et al, 1980;Szechtman et al, 1994b;Szumlinski et al, 1997). One hypothesis suggests that sensitization reflects a tolerance of the drug depressive effects (Baker and Tiffany, 1985;Hinson and Siegel, 1983) possibly due to the subsensitivity of presynaptic dopamine receptors (Antelman and Chiodo, 1983;Castro et al, 1985;Muller and Seeman, 1979;Richtand et al, 2001).…”

Section: Introductionmentioning

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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Section: Effect Of U69593 On Expression Of Sensitization To Qnpsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 99%

Section: Drugsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Moreover, the expression of both stimulantinduced locomotion and stereotypy can become conditioned to the environment in which the drug is administered with repeated drug administration (Badiani et al, 2000;Badiani and Robinson, 2004;Browman et al, 1998;Pert et al, 1990;Robinson et al, 1998;Szumlinski et al, 1997). Thus, to determine whether or not PPA pretreatment altered the expression of cocaine-induced stereotypy and to assess the potential role for conditioned factors in mediating the observed effects of PPA pretreatment upon cocaineinduced locomotor sensitization, groups of mice were pretreated with either saline control or 40 mg/kg PPA during PNDs 21-30.…”

Section: Cocaine-induced Stereotypymentioning

confidence: 99%

Protracted ‘Pro-Addictive’ Phenotype Produced in Mice by Pre-Adolescent Phenylpropanolamine

Szumlinski

Liu

Penzner

et al. 2007

Neuropsychopharmacol

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For decades, the sympathomimetic phenylpropanolamine (PPA; 7-norepinephrine) was an active ingredient found in popular children's over-the-counter (OTC) cold, cough, and allergy medications. To examine the possibility that pre-adolescent PPA exposure may induce neuroadaptations that influence behavioral and neurochemical responding to cocaine, C57BL/6J mice were pretreated with PPA (0-40 mg/kg) during postnatal days 21-31. The behavioral and neurochemical responses to acute and repeated cocaine (4 Â 15 mg/kg) were then assessed in adulthood when the mice were 10 weeks of age. Whereas pre-adolescent PPA exposure did not influence the acute locomotor response to 15 mg/kg cocaine, PPA pre-exposure dose-dependently enhanced the expression of cocaine-induced place conditioning, reduced the expression of locomotor sensitization, but did not influence cocaine-induced stereotypy. Pre-adolescent PPA exposure completely prevented the capacity of cocaine to elevate extracellular levels of catecholamines in the nucleus accumbens, but facilitated the development of cocaine-induced glutamate sensitization. Neither acute nor repeated cocaine altered extracellular GABA levels in the accumbens of control mice; however, 15 mg/kg cocaine lowered GABA levels by approximately 40% in PPA pretreated mice and this effect showed tolerance with repeated cocaine administration. These data provide the first evidence that early exposure to an OTC compound produces protracted effects upon cocaine-induced changes in nucleus accumbens neurotransmission that may contribute to a 'pro-addictive' phenotype in adulthood.

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Asymmetric modulation of a catecholamine‐regulated protein in the rat brain, following quinpirole administration

Gabriele

Culver

Sharma

et al. 2003

Synapse

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We previously reported a brain-specific 40 kDa catecholamine-regulated protein (CRP40) that binds dopamine (DA) and related catecholamines. CPR40 shares significant sequence homology with human heat shock protein (Hsp70), GRP78/BIP, and human #BQ24193 protein. Recent studies with the DA D(2) receptor antagonist, haloperidol, demonstrated a significant increase in expression of CRP40 in the striatum (STR). The objective of the present study was to investigate CRP40 expression in various brain regions following treatments with the DA D(2)/D(3) receptor agonist quinpirole (QNP) in rats and examine possible relationships between neurochemical parameters and locomotor activity. Rats received injections of either QNP (0.5 mg/kg, for 27 days every third day) or saline (SAL) and their locomotor activities were measured for 90 min after each injection. At injection 9, QNP-treated rats showed locomotor activity that was significantly greater than SAL controls (F(2,28) = 3.88, P < 0.05, Duncan's multiple range test, P < 0.05). Neurochemically, acute QNP-treated rats demonstrated significant differential expression of CRP40 in the left/right prefrontal cortex (PFC) relative to SAL-treated rats (-17.76 +/- 2.10%, -10.35 +/- 1.23%, P < 0.001). Chronic QNP significantly decreased CRP40 expression in the STR, ventral tegmental area (VTA), and left/right PFC (-24.85+/- 2.10%, -18.15 +/- 5.64%, -49.13 +/- 7.05%, -25 +/- 3.63%, P < 0.001). Finally, chronic QNP treatment resulted in a significant increase in CRP40 levels in the nucleus accumbens (NA) (+39.32 +/- 7.00%, P < 0.001). Heat shock protein (i.e., Hsp70 or Hsc70) expression remained unaltered following QNP treatment. Since QNP is a DA D(2)/D(3) agonist, alterations in CRP40 expression following QNP treatment suggest the protein's function in dopaminergic neurotransmission.

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Locomotor sensitization to quinpirole: environment-modulated increase in efficacy and context-dependent increase in potency

Cited by 64 publications

References 48 publications

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

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

Protracted ‘Pro-Addictive’ Phenotype Produced in Mice by Pre-Adolescent Phenylpropanolamine

Asymmetric modulation of a catecholamine‐regulated protein in the rat brain, following quinpirole administration

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