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The Journal of Neuroscience, May 4, 2005, 25(18):4453-4462; doi:10.1523/JNEUROSCI.4807-04.2005

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Behavioral/Systems/Cognitive
Maternal Deprivation Increases Vulnerability to Morphine Dependence and Disturbs the Enkephalinergic System in Adulthood

Vincent Vazquez,¹ Jacqueline Penit-Soria,² Claudette Durand,² Marie Jo Besson,² Bruno Giros,¹ and Valérie Daugé¹

¹Institut National de la Santé et de la Recherche Médicale, U513, Laboratoire de Neurobiologie et Psychiatrie, Université Paris XII, Faculté de Médecine, 94010 Créteil, France, and ²Centre National de la Recherche Scientifique, Unité Mixte de Recherche 7624, Laboratoire de Neurochimie Anatomie Institut des Neurosciences, Université ParisVI, 75005 Paris, France

Maternal deprivation can trigger long-lasting molecular and cellular modifications in brain functions and might facilitate the appearance of pathogenic behaviors. This study focuses on the vulnerability to develop morphine dependence in adult rats that were separated from their mother and littermates for 3 h per day for 14 d after birth and examines the adaptive changes in the enkephalinergic pathways. Place-preference conditioning was observed with 2 mg/kg morphine in deprived rats, whereas 5 mg/kg morphine was necessary to induce conditioning in nondeprived animals. A prolonged morphine conditioning was shown in deprived rats. A strong increase in oral morphine self-administration behavior and preference was observed in deprived rats. Only a very slight increase in preference for sucrose solution, a more ethological reinforcer known to interact with the opioid system, was shown in deprived rats. These results indicate that this postnatal environment change leads to a hypersensitivity to the reinforcing properties of morphine and to the development of morphine dependence. A significant decrease in preproenkephalin mRNA expression was observed in the nucleus accumbens and the caudate-putamen nucleus of deprived rats. The basal extracellular levels of the Met-enkephalin-like immunoreactivity in the nucleus accumbens were significantly lower in deprived rats when compared with nondeprived animals, whereas no change in µ-opioid receptor binding occurred. These results strongly support that maternal deprivation leads to a basal hypoactivity of the enkephalinergic system and hypersensitivity to morphine effects.

Together, our results suggest that maternal deprivation in pups likely represents a risk factor for morphine dependence in adult rats.

Key words: maternal deprivation; oral morphine and sucrose self-administration; place-preference paradigm; preproenkephalin mRNA; extracellular Met-enkephalin; µ-opioid receptors

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Received Nov 24, 2004; revised March 9, 2005; accepted March 15, 2005.

This article has been cited by other articles:

				C. C. Michaels and S. G. Holtzman Early Postnatal Stress Alters Place Conditioning to Both {micro}- and {kappa}-Opioid Agonists J. Pharmacol. Exp. Ther., April 1, 2008; 325(1): 313 - 318. [Abstract] [Full Text] [PDF]

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