Neurochemical changes in the striatum of dyskinetic rats after administration of the cannabinoid agonist WIN55,212-2

被引:38
作者
Morgese, M. G. [1 ,2 ]
Cassano, T. [1 ]
Gaetani, S. [3 ]
Macheda, T. [1 ]
Laconca, L. [1 ,3 ]
Dipasquale, P. [3 ]
Ferraro, L. [4 ]
Antonelli, T. [4 ]
Cuomo, V. [3 ]
Giuffrida, A. [2 ]
机构
[1] Univ Foggia, Dept Biomed Sci, I-71100 Foggia, Italy
[2] Univ Texas Hlth Sci Ctr San Antonio, Dept Pharmacol, San Antonio, TX 78229 USA
[3] Univ Roma La Sapienza, Dept Physiol & Pharmacol, Rome, Italy
[4] Univ Ferrara, Dept Clin & Expt Med, I-44100 Ferrara, Italy
关键词
6-Hydroxydopamine; Dopamine; Glutamate; Parkinson's disease; Microdialysis; DOPA-INDUCED DYSKINESIA; LONG-TERM DEPRESSION; PARKINSONS-DISEASE; BASAL GANGLIA; ENDOCANNABINOID RELEASE; CB1; RECEPTOR; CONCURRENT STIMULATION; SYNAPTIC-TRANSMISSION; CELLULAR-PARAMETERS; CYCLIC-AMP;
D O I
10.1016/j.neuint.2008.10.007
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Chronic use of levodopa, the most effective treatment for Parkinson's disease, causes abnormal involuntary movements named dyskinesias, which are linked to maladaptive changes in plasticity and disturbances of dopamine and glutamate neurotransmission in the basal ganglia. Dyskinesias can be modeled in rats with unilateral 6-hydroxydopamine lesions by repeated administration of low doses of levodopa (6 mg/kg, s.c.). Previous studies from our lab showed that sub-chronic treatment with the cannabinoid agonist WIN55,212-2 attenuates levodopa-induced dyskinesias at doses that do not interfere with physiological motor function. To investigate the neurochemical changes underlying WIN55,212-2 anti-dyskinetic effects, we used in vivo microdialysis to monitor extracellular dopamine and glutamate in the dorsal striatum of both the hemispheres of freely moving 6-hydroxydopamine-treated, SHAM-operated and intact rats receiving levodopa acutely or chronically (11 days), and studied how sub-chronic WIN55,212-2 (1 injection x 3 days, 20 min before levodopa) affected these neurochemical outputs. Our data indicate that: (1) the 6-hydroxydopamine lesion decreases dopamine turnover in the denervated striatum; (2) levodopa injection reduces extracellular glutamate in the side ipsilateral to the lesion of dyskinetic rats: (3) sub-chronic WIN55,212-2 prevents levodopa-induced glutamate volume transmission unbalances across the two hemispheres: and (4) levodopa-induced dyskinesias are inversely correlated with glutamate levels in the denervated striatum. These data indicate that the antidyskinetic properties of WIN55,212-2 are accompanied by changes of dopamine and glutamate outputs in the two brain hemispheres of 6-hydroxydopamine-treated rats. (C) 2008 Elsevier Ltd. All rights reserved.
引用
收藏
页码:56 / 64
页数:9
相关论文
共 81 条
  • [21] Role of cyclic AMP in the actions of cannabinoid receptors
    Childers, SR
    Deadwyler, SA
    [J]. BIOCHEMICAL PHARMACOLOGY, 1996, 52 (06) : 819 - 827
  • [22] Reciprocal inhibition of G-protein signaling is induced by CB1 cannabinoid and GABAB receptor interactions in rat hippocampal membranes
    Cinar, Resat
    Freund, Tamas F.
    Katona, Istvan
    Mackie, Ken
    Szucs, Maria
    [J]. NEUROCHEMISTRY INTERNATIONAL, 2008, 52 (08) : 1402 - 1409
  • [23] Di Monte DA, 2000, MOVEMENT DISORD, V15, P459, DOI 10.1002/1531-8257(200005)15:3<459::AID-MDS1006>3.0.CO
  • [24] 2-3
  • [25] Cannabinoid receptor type 1 located on presynaptic terminals of principal neurons in the forebrain controls glutamatergic synaptic transmission
    Domenici, Maria R.
    Azad, Shahnaz C.
    Marsicano, Giovanni
    Schierloh, Anja
    Wotjak, Carsten T.
    Dodt, Hans-Ulrich
    Zieglgaensberger, Walter
    Lutz, Beat
    Rammes, Gerhard
    [J]. JOURNAL OF NEUROSCIENCE, 2006, 26 (21) : 5794 - 5799
  • [26] The cannabinoid receptor agonist WIN 55,212-2 regulates glutamate transmission in rat cerebral cortex:: an in vivo and in vitro study
    Ferraro, L
    Tomasini, MC
    Gessa, GL
    Bebe, BW
    Tanganelli, S
    Antonelli, T
    [J]. CEREBRAL CORTEX, 2001, 11 (08) : 728 - 733
  • [27] Effects of levodopa on endocannabinoid levels in rat basal ganglia: implications for the treatment of levodopa-induced dyskinesias
    Ferrer, B
    Asbrock, N
    Kathuria, S
    Piomelli, D
    Giuffrida, A
    [J]. EUROPEAN JOURNAL OF NEUROSCIENCE, 2003, 18 (06) : 1607 - 1614
  • [28] Cannabinoids depress excitatory neurotransmission between the subthalamic nucleus and the globus pallidus
    Freiman, I
    Szabo, B
    [J]. NEUROSCIENCE, 2005, 133 (01) : 305 - 313
  • [29] Cannabinoids excite dopamine neurons in the ventral tegmentum and substantia nigra
    French, ED
    Dillon, K
    Wu, XF
    [J]. NEUROREPORT, 1997, 8 (03) : 649 - 652
  • [30] CB1 cannabinoid receptor inhibits synaptic release of glutamate in rat dorsolateral striatum
    Gerdeman, G
    Lovinger, DM
    [J]. JOURNAL OF NEUROPHYSIOLOGY, 2001, 85 (01) : 468 - 471