Archival ReportPeroxisome Proliferator-Activated Receptors-Alpha Modulate Dopamine Cell Activity Through Nicotinic Receptors
Section snippets
Methods and Materials
All procedures were performed in accordance with the Guidelines for the Care and Use of Mammals in Neuroscience and Behavioral Research (National Research Council 2004), EEC Council Directive (219/1990 and 220/1990) and approved by Animalerie Centrale and Médecine du Travail, Institut Pasteur. We made all efforts to minimize pain and suffering and to reduce the number of animals used.
The PPARα Antagonist MK886 Enhances DA Neuron Spontaneous Activity
To characterize the postsynaptic effects on DA neurons, all experiments were performed in the presence of CNQX (10 μmol/L), D-AP5 (100 μmol/L), and picrotoxin (100 μmol/L) to block alpha-Amino-3-hydroxy-5-methyl-4-isoxazole propionic acid-, N-methyl-D-aspartate-, and gamma-aminobutyric acidA-mediated postsynaptic responses. Whole-cell current- and voltage-clamp recordings were performed from medial posterior VTA DA neurons in rat horizontal slices containing the midbrain. The DA cells displayed
Discussion
Here we show that PPARα significantly contributes to the effects of endogenous cholinergic transmission mediated by β2-nAChRs on DA neuron excitability and to the effects of nicotine on locomotor activity, a DA associated behavior. The changes in number of spontaneously active DA neurons in vivo following PPARα activation are consistent with both the decreased spontaneous activity of individual VTA DA neurons and the diminished VTA net output observed in vitro. A functional consequence of
References (55)
Behavioral dopamine signals
Trends Neurosci
(2007)- et al.
Afferent modulation of dopamine neuron firing patterns
Curr Opin Neurobiol
(1999) - et al.
Autoradiographic localization of M1 and M2 muscarine receptors in the rat brain
Neuroscience
(1986) - et al.
Preferential stimulation of ventral tegmental area dopaminergic neurons by nicotine
Eur J Pharmacol
(1987) - et al.
Hierarchical control of dopamine neuron-firing patterns by nicotinic receptors
Neuron
(2006) - et al.
Mesopontine neurons in schizophrenia
Neuroscience
(1995) - et al.
Isolation and characterization of peroxisome proliferator-activated receptor (PPAR) interacting protein (PRIP) as a coactivator for PPAR
J Biol Chem
(2000) - et al.
Protective activation of the endocannabinoid system during ischemia in dopamine neurons
Neurobiol Dis
(2006) - et al.
The cyclo-oxygenase inhibitor nimesulide induces conditioned place preference in rats
Eur J Pharmacol
(2000) - et al.
Electrophysiological characterization of nicotine-induced excitation of dopaminergic neurons in the rat substantia nigra
J Pharmacol Sci
(2003)