In vivo evidence of D3 dopamine receptor sensitization in parkinsonian primates and rodents with l-DOPA-induced dyskinesias
Section snippets
Rodent studies
All animal studies were performed following NIH guidelines and were approved by the IACUC at McLean Hospital and Harvard Medical Area. Naïve and 6-OHDA-lesioned adult female Sprague-Dawley rats (200–250 g) were purchased from Charles River Laboratories and Taconic. The animals were unilaterally lesioned by 6-OHDA injection (4 μl; 2 μg/μl) into the medial forebrain bundle. An appropriate level of denervation was evaluated by the rotational response to apomorphine (0.05 mg/kg) and amphetamine
Effects of DA denervation and chronic l-DOPA administration on the rCBV response to 7-OHDPAT in 6-OHDA-lesioned hemiparkinsonian rats
In naïve anesthetized rats 7-OHDPAT administration induced a negative change in rCBV in the nucleus accumbens (Figs. 1a–b) (Choi et al., 2006) corresponding to the anatomical distribution of the D3 receptor (Murray et al., 1994), which is highly expressed in the ventromedial shell of the nucleus accumbens, olfactory tubercle and islands of Calleja and low in the motor striatum (Sokoloff et al., 1990). The hemodynamic changes induced by 7-OHDPAT in the nucleus accumbens were larger than the
Discussion
In this study we examined in vivo dynamic changes in response to 7-OHDPAT using phMRI in naïve, parkinsonian and l-DOPA-treated, dyskinetic animals. We used 2 complementary models: the unilateral acute 6-OHDA rodent model that, although not without limitations as a model for dyskinesia, is quite informative and allow us to compare this study with our previous studies mapping normal distribution of DA receptors in the rodent brain, and a bilateral primate model that closely resembles PD and the l
Acknowledgments
We are grateful to Jack McDowell and Jennifer Pagel for excellent technical help and to Dr Anna Liisa Brownell and staff in her lab for the PET studies. This work was supported by the NINDS P50 NS-39793 and N.E.R.P.R.C. Center Grant P51RR00168.
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