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Intrastriatal 6-OHDA Lesion Differentially Affects Dopaminergic Neurons in the Ventral Tegmental Area of Prenatally Stressed Rats

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Abstract

Exposure to a variety of stressful events during the last week of pregnancy in rats interferes with the correct progeny development, which in turn leads to delays in motor development, impaired adaptation to stressful conditions, altered sexual behaviour, learning deficits, neuronal development and brain morphology. Many of these alterations have been attributed to changes in dopamine (DA) neurotransmission and occur primarily in the mesolimbic system. We found that prenatally stressed offspring showed higher levels of cells expressing tyrosine hydroxylase (TH) in the ventral tegmental area (VTA) and that these cells were more susceptible to a neurochemical insult with 6-hydroxy-DA (6-OHDA) in adulthood. Moreover, prenatally stressed rats presented differences in terms of the number and asymmetry of neuronal nitric oxide synthase-expressing cells in the VTA and nucleus accumbens, respectively. Similar to the results described for TH-expressing cells, the nitrergic systems were differentially regulated after 6-OHDA lesion in control and prenatally stressed rats. These results indicated that prenatal stress affects the dopaminergic and nitrergic systems in the mesolimbic pathway. In addition, we propose that the mesolimbic areas are more susceptible than the motor areas to a neurochemical insult during adult life.

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Acknowledgments

The authors wish to thank Dr. Ana Maria Adamo and Ms. María Florencia Almeira Gubiani (Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina) for their valuable assistance in the stereotaxical experiments as well as Mr. Majid Amar (INSERM UMRS 975, CRICM, ICM, Thérapeutique Expérimentale de la Neurodégénérescence, Paris, France) for his assistance in IHC experiments. We are also indebted to Martin Brahamian and Mercedes Imsem (Universidad de Buenos Aires, Buenos Aires, Argentina) for their help and supervision in the management and care of the rats. The skilful technical assistance of Mrs. Susana Buglione (Instituto de Química y Fisicoquímica Biológicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Buenos Aires, Argentina) is greatly appreciated. This research was supported by Grants from CONICET (PIP 2065), ANPCYT (PICT 31981 and PICT 0040), and Bernardo Houssay Program (CONICET/MINCyT/France Embassy).

Conflicts of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Author notes

  1. María Eugenia Pallarés & Marta C. Antonelli

    Present address: Instituto de Biología Celular y Neurociencias “Prof. Eduardo De Robertis”, Paraguay 2155, piso 3, Universidad de Buenos Aires, C1121ABG, Buenos Aires, Argentina

  2. Carlos J. Baier

    Present address: Instituto de Investigaciones Bioquímicas de Bahía Blanca, B8000FWB, Bahía Blanca, Argentina

  3. María R. Katunar

    Present address: División Corrosión - INTEMA - Facultad de Ingeniería, Universidad Nacional de Mar del Plata, Juan B. Justo 4302, B7608FDQ, Mar del Plata, Buenos Aires, Argentina

Authors and Affiliations

  1. Instituto de Química y Fisicoquímica Biológicas (UBA-CONICET), Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Junín 956, C1113AAD, Buenos Aires, Argentina

    Carlos J. Baier, María Eugenia Pallarés, Ezequiela Adrover, María R. Katunar & Marta C. Antonelli

  2. INSERM UMRS 975, CRICM, ICM, Thérapeutique Expérimentale de la Neurodégénérescence, Paris, France

    Rita Raisman-Vozari

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Baier, C.J., Pallarés, M.E., Adrover, E. et al. Intrastriatal 6-OHDA Lesion Differentially Affects Dopaminergic Neurons in the Ventral Tegmental Area of Prenatally Stressed Rats. Neurotox Res 26, 274–284 (2014). https://doi.org/10.1007/s12640-014-9479-7

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