Environmental stimulation reduces the rewarding effects of cocaine and heroin
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1
University of Poitiers, CNRS UMR 6187, Institut de Physiologie et Biologie Cellulaires, France
Environmental manipulations during adolescence, a critical period of development, can have important consequences on subsequent vulnerability to drugs of abuse. Whereas many studies have demonstrated that negative environmental conditions increase vulnerability to drugs, little is known on whether positive environmental conditions such as enriched environments (EE) have protective effects against addiction. EE are known to enhance sensory, cognitive and motor stimulation in addition to increase learning and memory, facilitate recovery from brain injuries and to reduce the insurgence of neurodegenerative disorders.
This poster will summarize our recent findings obtained in mice raised in an EE and subjected to protocols aimed at measuring the locomoter and rewarding effects of addictive drugs such as cocaine and heroine. Our EE setup consisted of housing cages that were bigger than standard cages and contained constantly a running wheel and a small house and four-five toys that were changed once a week with new toys of different shape and color.
EE mice showed several alterations in the levels of mRNA coding for proteins involved in cell proliferation, cell differentiation, signal transduction, transcription and translation, cell structure and metabolism, as evidenced by cDNA arrays and real-time quantitative PCR. Some of these results (Pkc Lambda) were also confirmed at the protein level. These alterations may be involved in the differential response of EE mice to addictive drugs. Indeed, mice exposed to EE from weaning to adulthood show a decrease in cocaine-induced locomotor activity. In addition we showed that the rewarding effects of both cocaine (10 and 20 mg/kg i.p.) and heroin (1 and 2 mg/kg s.c.) were blunted in EE mice compared to SE mice raised in a standard environment (SE) as measured by conditioned place preference paradigm. Furthermore, EE mice were protected against the sensitizing effects of cocaine (15 mg/kg) but not of heroin (1 mg/kg). Both cocaine- and heroin-induced increases in dopamine levels in the nucleus accumbens did not differ between EE and SE mice as measured by in vivo microdialysis. Using in situ hybridization, we found that cocaine- but not heroin-induced increases in the expression of the immediate early gene zif-268 in the nucleus accumbens were blunted in EE mice compared to SE mice.
Altogether, our results demonstrate that EE can protect against the rewarding effects of cocaine and heroin. However, whereas the sensitizing effects of cocaine were reduced by EE, those of heroin were not. Thus, as previously reported, the effects of cocaine and heroin appear to be affected differently by experimental manipulations. In the case of cocaine, activating and rewarding effects appear to be mediated by similar substrates and in the particular by the nucleus accumbens whereas in the case of heroin rewarding effects appear to be independent on activation of the mesolimbic system. Notwithstanding these differences, the fact that the rewarding effects of cocaine and heroin were both reduced by EE highlights the importance of providing positive environmental conditions during early stages of life in order to reduce vulnerability to drug addiction.
Conference:
3rd Mediterranean Conference of Neuroscience , Alexandria, Egypt, 13 Dec - 16 Dec, 2009.
Presentation Type:
Poster Presentation
Topic:
Aging & Environment
Citation:
Jaber
M,
Thiriet
N,
Rawas
RE,
Chauvet
C,
Lardeux
V and
Solinas
M
(2009). Environmental stimulation reduces the rewarding effects of cocaine and heroin.
Front. Neurosci.
Conference Abstract:
3rd Mediterranean Conference of Neuroscience .
doi: 10.3389/conf.neuro.01.2009.16.182
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Received:
29 Nov 2009;
Published Online:
29 Nov 2009.
*
Correspondence:
Mohamed Jaber, University of Poitiers, CNRS UMR 6187, Institut de Physiologie et Biologie Cellulaires, 86022 Poitiers, France, mohamed.jaber@univ-poitiers.fr