Long-term sensitization of apomorphine-induced rotation behavior in rats with dopamine deafferentation or excitotoxin lesions of the striatum

Ex vivo [11C]‐(+)‐PHNO binding is unchanged in animal models displaying increased high‐affinity states of the D2receptor in vitro

“…We examine [ 11 C]-(þ)-PHNO and [ 3 H]-raclopride SBR in AMPH-sensitized, ethanol-withdrawn and unilaterally 6-OHDA-lesioned rats. Dopaminergic supersensitivity, common to all three of these animal models (Castner and Goldman-Rakic, 2003;Castner et al, 2000;Costall et al, 1976;Itzhak and Martin, 1999;Klug and Norman, 1993;Lessov and Phillips, 1998;Manley and Little, 1997;Mileson et al, 1991;Patrick et al, 1991;Robinson and Becker, 1986;Sams-Dodd, 1998;Schwarting and Huston, 1996a,b;Tenn et al, 2003), is associated, in vitro, with large increases in the proportion of D 2 receptors in the high-affinity state (Seeman et al, 2005b). In two of the models examined here-AMPHsensitized and ethanol-withdrawn rats-360% increases in the high-affinity state has been directly measured using in vitro competitive binding experiments in striatal membrane preparations (Seeman et al, 2002(Seeman et al, , 2004(Seeman et al, , 2005b.…”

“…The basis for this examination stems from in vitro work showing that in animal models, dopaminergic supersensitivity is associated with a large increase in the proportion of D 2 receptors in the high-affinity state (Briand et al, 2008;Samaha et al, 2007;Seeman et al, 2002Seeman et al, , 2004Seeman et al, , 2005bSeeman et al, , 2007. The current study examines the SBR of the agonist radiotracer [ 11 C]-(þ)-PHNO and the antagonist radiotracer [ 3 H]-raclopride in three such animal models: amphetamine-sensitized rats Goldman-Rakic, 1999, 2003;Patrick et al, 1991;Robinson and Becker, 1986;Sams-Dodd, 1998;Tenn et al, 2003), rats withdrawn from chronic ethanol (Itzhak and Martin, 1999;Lessov and Phillips, 1998;Manley and Little, 1997), and unilaterally 6-OHDAlesioned rats (Costall et al, 1976;Klug and Norman, 1993;Mileson et al, 1991;Schwarting and Huston, 1996a,b). All of these animal models display dopaminergic supersensitivity and in two of them-ampheta-mine-sensitized and ethanol-withdrawn rats-the in vitro increase in high-affinity state has been directly measured using competitive binding experiments (Seeman et al, 2002(Seeman et al, , 2004(Seeman et al, , 2005b.…”

Evaluation of the Integrity of the Dopamine System in a Rodent Model of Parkinson’s Disease: Small Animal Positron Emission Tomography Compared to Behavioral Assessment and Autoradiography

“…In the past, longitudinal assessment of this model depended primarily on repeated pharmacological challenges [2], which in themselves can modify the system. The best of example of this is the robust observation of sensitization of both the Correspondence to: Elissa M. Strome; e-mail: strome@interchange.ubc.ca behavioral response and the D 1 receptor after repeated apomorphine [3,4]. The 6-OHDA rat model is therefore a good example of an animal model of a human disease that can greatly benefit from advances in our ability to reliably, reproducibly, and sensitively evaluate longitudinally, in vivo, the disease process or the effects of therapeutics.…”

The D1receptor‐mediated effects of the ergoline derivative LEK‐8829 in rats with unilateral 6‐hydroxydopamine lesions

“…The intense response to the drug developed after previous sensitization (priming) with apomorphine. The sensitization of the turning response induced by apomorphine has been described previously (Morelli et al, 1989;Klug & Norman, 1993). The response to LEK-8829 stabilized after repeated weakly applications, both in duration and intensity (rotational speed) of the turning response.…”

“…The intense response to the drug developed after previous sensitization (priming) with apomorphine. The sensitization of the turning response induced by apomorphine has been described previously (Morelli et al, 1989;Klug & Norman, 1993 (Krisch et al, 1994), showing higher affinity of LEK-8829 for D2 as compared to DI receptors. The probable explanation for the differences between the in vitro affinities and in vivo effective doses of the drug may be in the presence of a high proportion of spare DI receptors in the striatum (Battaglia 1986;Watts et al, 1995 .…”