Cocaine sensitization does not alter SP effects on locomotion or excitatory synaptic transmission in the NAc of rats

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DOIResolve DOI: http://doi.org/10.1016/j.neuropharm.2011.09.008
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TypeArticle
Journal titleNeuropharmacology
ISSN00283908
Volume62
Issue2
Pages825832
SubjectSubstance abuse; Cocaine; Substance P; Excitatory postsynaptic currents; Synaptic plasticity; Neuropeptides
AbstractSubstance P (SP) and cocaine employ similar mechanisms to modify excitatory synaptic transmission in the nucleus accumbens (NAc), a region implicated in substance abuse. Here we explored, using NAc slices, whether SP effects on these synaptic responses were altered in rats that have been sensitized to cocaine and whether SP could mimic cocaine in triggering increased locomotion in sensitized rats. Intraperitoneal (IP) injection of naïve rats with cocaine (15 mg/kg) caused increased locomotion by 408.5 ± 85.9% (n = 5) which further increased by 733.1 ± 157.8% (n = 5) following a week of cocaine sensitization. A similar challenge with 10 mg/kg of SP after cocaine sensitization did not produce significant changes in locomotion (170.6 ± 61.0%; n = 4). In contrast to cocaine, IP injection of rats with SP or SP5–11 (10–100 mg/kg) with or without phosphoramidon did not elicit changes in locomotion. In electrophysiological studies, both cocaine and SP depressed evoked NMDA and non-NMDA receptor-mediated excitatory synaptic currents (EPSCs) in slices obtained from naïve rats. In slices derived from cocaine-sensitized rats, cocaine but not SP produced a more profound decrease in non-NMDA compared to NMDA responses. Similar to that in naïve rats, cocaine’s effect on the EPSCs in these sensitized rats occluded those of SP. Thus, although SP and cocaine may employ similar mechanisms to depress EPSCs in the NAc, IP injection of SP does not mimic cocaine-induced hyperlocomotion indicating that not all of cocaine’s effects are mimicked by SP.
Publication date
LanguageEnglish
AffiliationNRC Institute for Nutrisciences and Health; National Research Council Canada
Peer reviewedYes
IdentifierS0028390811004023
NPARC number21268826
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Record identifieradc1dff7-db22-4cb7-882a-00d87e5ed4be
Record created2013-11-14
Record modified2016-05-09
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