Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2014 Dec 7;18(5):pyu088.
doi: 10.1093/ijnp/pyu088.

Temporal regulation of peripheral BDNF levels during cocaine and morphine withdrawal: comparison with a natural reward

Hélène Anne-Sophie Geoffroy  1 , Stephanie Puig  1 , Nadia Benturquia  1 , Florence Noble  2
Affiliations

Temporal regulation of peripheral BDNF levels during cocaine and morphine withdrawal: comparison with a natural reward

Hélène Anne-Sophie Geoffroy et al. Int J Neuropsychopharmacol. .

Abstract

Background: Brain-derived neurotrophic factor (BDNF) is a neurotrophin that has long been studied in the field of addiction and its importance in regulating drug addiction-related behavior has been widely demonstrated. The aim of our study was to analyze the consequences of a repeated exposure to drugs of abuse or natural reward on plasma BDNF levels during withdrawal.

Methods: Rats were chronically injected with morphine (subcutaneously, 5mg/kg) or cocaine (intraperitoneally, 20mg/kg) or fed with a butter biscuit (per os, 4g) once per day for 14 days. Blood collection was performed on the 1st (withdrawal day 1 or WD1) or on (WD14), either at the same time point rats had been exposed to drugs or natural reward or at a different time point (used to quantify basal brain-derived neurotrophic factor levels).

Results: Cocaine treatment led to a rapid (WD1) and persistent (WD14) decrease of basal BDNF levels compared with saline-treated animals, whereas morphine induced an increase on WD14 without any alteration on WD1. On the contrary, the natural reward induced a significant increase of basal brain-derived neurotrophic factor levels only on WD1. The analysis of BDNF levels at the usual time point at which animals had been exposed showed that both drugs, but not the natural reward, increased BDNF levels compared with basal levels.

Conclusion: Our data highlight that only drugs of abuse are able to persistently alter BDNF levels and to induce specific variations of this neurotrophic factor at the usual hour of injection.

Keywords: Brain-derived neurotrophic factor; cocaine; morphine; natural reward; plasma.

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
Experimental procedures. Each rat daily received butter biscuit or drug injections (morphine or cocaine) at the same hour every day for 14 days. On the 1st and 14th day after the end of the treatments, rats were sacrificed either at the usual hour of treatment or at another time, and plasma brain-derived neurotrophic factor (BDNF) levels were measured. D1, day 1; D14, day 14; WD1, withdrawal day 1; WD14, withdrawal day 14.
Figure 2.
Figure 2.
Brain-derived neurotrophic factor (BDNF) levels in control rats at the usual hour of saline injection and on a basal level on withdrawal day 1 (WD1). Each rat received 14 days of saline injection and was sacrificed either at the usual hour of injection or at another time of saline injection on WD1 (basal level). Data (mean ± SEM) are expressed as percent of BDNF level normalized to basal levels (n=6–10) and were compared by a 2-tailed Student t-test.
Figure 3.
Figure 3.
Basal brain-derived neurotrophic factor (BDNF) level in plasma after treatments on withdrawal day 1 (WD1) and withdrawal day 14 (WD14). Basal plasma BDNF levels were analyzed in animals that were treated with either cocaine (a, d) or morphine (b, e) or were given the natural reward (c, f) for 14 days. Plasma was collected 1 (a-c) or 14 (d-f) days after the end of treatments at hours that do not match with the usual hour of injection or food presentation (ie, in the afternoon). Data (mean ± SEM) are expressed as percent of BDNF levels normalized to the appropriate control (the group that received either saline injections or standard chow) (n=6–10). Means were compared by a 2-tailed Student t test. *P<.05, **P<.01; ***P<.001 vs control group.
Figure 4.
Figure 4.
Brain-derived neurotrophic factor (BDNF) level in plasma at the usual hour of injection or natural reward presentation on withdrawal day 1 (WD1) and withdrawal day 14 (WD14). Plasma BDNF levels were analyzed in animals that were treated with either cocaine (a, d) or morphine (b, e) or were given the natural reward (c, f) for 14 days. Plasma collection was realized 1 (a-c) or 14 (d-f) days after the end of the treatments either at the usual hour of injection (or food presentation) or at another time in the afternoon. Data (mean ± SEM) are expressed as percent of BDNF levels normalized to basal levels (rats receiving the corresponding treatment but sacrificed at another time than the usual drug injection or natural reward presentation; n=6–10). Means were compared by a 2-tailed Student t-test. *P<.05, ***P<.001 vs basal levels.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Aguiar-Nemer AS, Toffolo MCF, da Silva CJ, Laranjeira R, Silva-Fonseca VA. (2013). Leptin influence in craving and relapse of alcoholics and smokers. J Clin Med Res 5:164–167. - PMC - PubMed
    1. Autry AE, Monteggia LM. (2012). Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol Rev 64:238–258. - PMC - PubMed
    1. Badiani A, Belin D, Epstein D, Calu D, Shaham Y. (2011). Opiate versus psychostimulant addiction: the differences do matter. Nat Rev Neurosci 12:685–700. - PMC - PubMed
    1. Béjot Y, Mossiat C, Giroud M, Prigent-Tessier A, Marie C. (2011). Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies. PLoS ONE 6:e29405. - PMC - PubMed
    1. Bertani S, Carboni L, Criado A, Michielin F, Mangiarini L, Vicentini E. (2010). Circadian Profile of peripheral hormone levels in Sprague-Dawley rats and in common marmosets (Callithrix jacchus). In Vivo 24:827–836. - PubMed

LinkOut - more resources