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Administration of the calcineurin inhibitor cyclosporine modulates cocaine-induced locomotor activity in rats
- Source :
- Psychopharmacology. 200:129-139
- Publication Year :
- 2008
- Publisher :
- Springer Science and Business Media LLC, 2008.
-
Abstract
- Cocaine administration in rats increases locomotor activity as a result of underlying changes in neurotransmitter dynamics and intracellular signaling. The serine/ threonine phosphatase, calcineurin, is known to modulate several signaling proteins that can influence behavioral responses to cocaine.This study aimed to determine whether calcineurin plays a role in locomotor responses associated with acute and repeated cocaine exposure. Second, we examined cocaine-mediated changes in intracellular signaling to identify potential mechanism underlying the ability of calcineurin to influence cocaine-mediated behavior.Locomotor activity was assessed over 17 days in male Sprague-Dawley rats (n = 48) that received daily administration of cocaine (15 mg/kg, s.c.) or saline in the presence or absence of the calcineurin inhibitor, cyclosporine (15 mg/kg, i.p.). Non-cocaine-treated animals from this initial experiment (n = 24) also received an acute cocaine challenge on day 18 of testing.Daily cyclosporine administration potentiated the locomotor response to repeated cocaine 5 min after cocaine injection and attenuated the sustained locomotor response 15 to 40 min after cocaine. Furthermore, cyclosporine pretreatment for 17 days augmented the acute locomotor response to acute cocaine 5 to 30 min after cocaine injection. Finally, repeated exposure to either cocaine or cyclosporine for 22 days increased synapsin I phosphorylation at the calcineurin-sensitive Ser 62/67 site, demonstrating a common downstream target for both calcineurin and cocaine.Our results suggest that calcineurin inhibition augments locomotor responses to cocaine and mimics cocaine-mediated phosphorylation of synapsin I.
- Subjects :
- Male
medicine.medical_specialty
Time Factors
Calcineurin Inhibitors
Motor Activity
Pharmacology
Biology
Nucleus accumbens
Article
Rats, Sprague-Dawley
Serine
chemistry.chemical_compound
Cocaine
Internal medicine
medicine
Animals
Phosphorylation
Neurotransmitter
Behavior, Animal
Calcineurin
Synapsin
Synapsins
Rats
Endocrinology
chemistry
Cyclosporine
Signal transduction
Intracellular
Signal Transduction
Subjects
Details
- ISSN :
- 14322072 and 00333158
- Volume :
- 200
- Database :
- OpenAIRE
- Journal :
- Psychopharmacology
- Accession number :
- edsair.doi.dedup.....da771dc48ef184ba545741f8f46cdb02