Mifepristone and spironolactone differently alter cocaine intravenous self-administration and cocaine-induced locomotion in C57BL/6J mice.
Addiction Biology. 2010-01-01; 15(1): 81-87
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1. Addict Biol. 2010 Jan;15(1):81-7. doi: 10.1111/j.1369-1600.2009.00178.x.
Mifepristone and spironolactone differently alter cocaine intravenous
self-administration and cocaine-induced locomotion in C57BL/6J mice.
Fiancette JF(1), Balado E, Piazza PV, Deroche-Gamonet V.
(1)INSERM U862, NeuroCentre Magendie, 146 rue Léo Saignat, Bordeaux Cedex,
Corticosterone, the main glucorticoid hormone in rodents, facilitates behavioral
responses to cocaine. Corticosterone is proposed to modulate cocaine intravenous
self-administration (SA) and cocaine-induced locomotion through distinct
receptors, the glucocorticoid receptor (GR) and the mineralocorticoid receptor
(MR), respectively. However, this remains debatable. On one hand, modulation of
both responses by the GR was tested in different experimental conditions, i.e.
light versus dark nycthemeral phase and naïve versus cocaine-experienced animals.
On the other hand, modulation of both responses by the MR was never tested
directly but only inferred based on the ability of low plasma corticosterone
levels (those for which corticosterone almost exclusively binds the MR) to
compensate the effects of adrenalectomy. Our goal here was to test the
involvement of the GR and the MR in cocaine-induced locomotor and reinforcing
effects in the same experimental conditions. C57Bl/6J mice were trained for
cocaine (1 mg/kg/infusion) intravenous SA over 40 SA sessions. The animals were
then administered with mifepristone (30 mg/kg i.p.), a GR antagonist, or with
spironolactone (20 mg/kg/i.p.), an MR antagonist, 2 hours before either cocaine
intravenous SA or cocaine-induced locomotion. In a comparable nycthemeral period
and in similarly cocaine-experienced animals, a blockade of the GR decreased
cocaine-induced reinforcing effects but not cocaine-induced locomotion. A
blockade of the MR decreased both cocaine-induced reinforcing (but to a much
lesser extent than the GR blockade) and locomotor effects. Altogether, our
results comforted the hypothesis that the GR modulates cocaine-related operant
conditioning, while the MR would modulate cocaine-related unconditioned effects.
The present data also reveal mifepristone as an interesting tool for manipulating
the impact of corticosterone on cocaine-induced reinforcing effects in mice.
PMID: 19799583 [Indexed for MEDLINE]