Prior D1 dopamine receptor stimulation is required to primeD2-mediated striatal Fos expression in 6-hydroxydopamine-lesioned rats
Section snippets
Drug treatments and behavioral recordings
Male Sprague–Dawley rats (Charles River Laboratories, Wilmington, MA) weighing 250–300 g were anesthetized with ketamine (50 mg/kg): xylazine (10 mg/kg) (1:1) and pretreated with desmethylimipramine (25 mg/kg, i.p.) to prevent damage to noradrenergic neurons. Four microliters of a saline solution containing 6-OHDA-HBr (3 mg/ml) and ascorbic acid (2 mg/ml) was infused into the left medial forebrain bundle at a rate of 1 μl/min (stereotaxic coordinates from bregma: −3.7 mm AP, +1.6 mm ML, and −8.8 mm DV)
Dopamine depletion following 6-hydroxydopamine lesion
Unilateral injection of 6-OHDA into the medial forebrain bundle lead to a profound reduction of striatal dopamine levels (t12=19.3, P<0.0001). These 6-OHDA rats exhibited >99% dopamine depletion in the ipsilateral striatum which was associated with robust 180° contralateral rotations following the first (364±47), second (405±91), and third (409±130) apomorphine (0.5 mg/kg) pretreatment injections. Previously, we have shown that these apomorphine-primed 6-OHDA rats also show a marked reduction of
Priming of quinpirole-mediated contralateral rotation and striatal Fos
In agreement with other reports, administration of quinpirole (0.25 mg/kg) did not induce contralateral rotation or striatal Fos expression in water-pretreated (unprimed) 6-OHDA rats.42., 48. However, three pretreatment injections with the D1/D2 agonist apomorphine (0.5 mg/kg) permitted the same dose of quinpirole to induce robust contralateral rotation in 6-OHDA rats, consistent with previous observations.3., 43., 48., 54. In addition, three apomorphine pretreatment injections permitted an
Conclusions
The present findings demonstrate that prior administration of D1, D2 or D1/D2 agonists to 6-OHDA-lesioned rats potentiates D2-mediated rotational behavior consistent with the priming response. However, prior treatment with a D1 agonist is required to prime D2-mediated striatal Fos expression in D1-expressing23., 29. striatoentopeduncular neurons48 that comprises the “direct” striatal output pathway.1 These data suggest that prior D1 receptor stimulation alters the responsiveness of the “direct”
Acknowledgements
We greatly appreciate the technical assistance of Saundra Patrick with the HPLC analyses and the statistical expertise of Drs Rebecca Burwell and William Heindel. This work was supported by funds from the American Parkinson Disease Association and Brown University.
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Cited by (20)
Abnormal involuntary movement (AIM) expression following D2 dopamine agonist challenge is determined by the nature of prior dopamine receptor stimulation (priming) in 6-hydroxydopamine lesioned rats
2013, Pharmacology Biochemistry and BehaviorCitation Excerpt :Thus, it may be that Quin (1 mg/kg)-primed 6-OHDA rats would have developed limb and grooming AIMs if they were treated over a longer time course, an effect that may have been hastened in our three-injection priming paradigm by using a higher dose of Quin (2.5 mg/kg). We have previously reported that while Quin (0.25 mg/kg) challenge did not induce rotational behavior in water-primed 6-OHDA rats, priming with Apo (0.5 mg/kg), SKF (10 mg/kg) or Quin (1 mg/kg) led to robust contralateral rotational behavior following Quin challenge (Pollack et al., 1997; Pollack and Thomas, 2010; Pollack and Yates, 1999). Similarly, in this study Quin challenge was unable to produce AIMs in water-primed 6-OHDA rats, whereas animals primed with Apo, SKF or Quin (1 or 2.5 mg/kg) exhibited combinations of axial, limb, locomotor or grooming AIMs.
Local modulation of striatal glutamate efflux by serotonin 1A receptor stimulation in dyskinetic, hemiparkinsonian rats
2011, Experimental NeurologyCitation Excerpt :Finally, a post-test with l-DOPA alone was performed at the end of the study to ensure stable AIMs throughout testing (Fig. 1). Three weeks after 6-OHDA (n = 10) or sham (n = 7) lesions of the MFB and unilateral striatal microdialysis cannulations, rats in the second experiment received injections of the D1R agonist SKF81297 (0.8 mg/kg, sc; Sigma), dissolved in 20% dimethyl sulfoxide (DMSO) in 0.9% NaCl, on 3 separate occasions 2–3 days apart in order to sensitize D1R (Pollack & Yates, 1999; Dupre et al., 2007). The dose of SKF81297 and priming regimen have been used in our lab to produce stable AIMs expression that is similar to the AIMs induced by our current dose of l-DOPA (Dupre et al., 2007; Dupre et al., 2008a).
D1 priming enhances both D1- and D2-mediated rotational behavior and striatal Fos expression in 6-hydroxydopamine lesioned rats
2010, Pharmacology Biochemistry and BehaviorThe differential effects of 5-HT<inf>1A</inf> receptor stimulation on dopamine receptor-mediated abnormal involuntary movements and rotations in the primed hemiparkinsonian rat
2007, Brain ResearchCitation Excerpt :A time course including surgery, drug administration and behavioral testing is shown in Fig. 1. Three weeks after 6-OHDA lesions, rats received injections of the D1R agonist R(+)-SKF-81297 hydrobromide (SKF81297; 0.8 mg/kg, i.p.; Sigma) on 3 separate occasions 2 to 3 days apart in order to sensitize both D1 and D2 receptors (Pollack and Yates, 1999). Contralateral rotations and AIMs (see description below) were observed immediately after injections.