Administration of the calcineurin inhibitor cyclosporine modulates cocaine-induced locomotor activity in rats
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
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.
- blah 213_2008_1189_Fig1_ESM.tif (1345KB)
- blah 213_2008_1189_Fig2_ESM.tif (493KB)
- blah 213_2008_1189_Fig3_ESM.tif (431KB)
- blah 213_2008_1189_Fig4_ESM.tif (748KB)
- blah 213_2008_1189_Fig1_ESM.gif (202KB)
- blah 213_2008_1189_Fig2_ESM.gif (50KB)
- blah 213_2008_1189_Fig3_ESM.gif (43KB)
- blah 213_2008_1189_Fig4_ESM.gif (53KB)
- Administration of the calcineurin inhibitor cyclosporine modulates cocaine-induced locomotor activity in rats
Volume 200, Issue 1 , pp 129-139
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Locomotor activity
- Nucleus accumbens
- Industry Sectors
- Author Affiliations
- 1. Interdepartmental Neuroscience Program, Yale University School of Medicine, New Haven, CT, 06508, USA
- 2. Department of Psychiatry, Yale University School of Medicine, New Haven, CT, 06508, USA
- 3. 34 Park Street, 3rd Floor Research, New Haven, CT, 06508, USA