Original articleJuvenile Administration of Methylphenidate Attenuates Adult Hippocampal Neurogenesis
Section snippets
Rats and Drug Treatment
Lactating female Sprague–Dawley rats with their male pups were purchased from Harlan (Indianapolis, Indiana). Pups were at D14 on arrival and were given 4 days of acclimation before weaning at D18. Drug treatment lasted for 16 days (D20–35), during which the rats received intraperitoneal (IP) injections twice a day (12 am and 6 pm) of either MPH hydrochloride (MPH HCl, 2.0 mg/kg, dissolved in .9% saline as 1 mL/kg, Sigma Laboratories, St. Louis, Missouri) or .9% saline vehicle injections (SAL,
Juvenile MPH Decreases Locomotor Response to Novelty in Adulthood
Locomotor activity in a novel environment was significantly different between SAL and MPH rats [Figure 1A;F(1,40) = 4.3, p < .05], with the D112 MPH rats displaying less locomotion compared with D112 SAL rats (p < .01). During the 90-min test, there was also a significant difference between MPH and SAL rats [F(1,9) = 8.1, p < .05], with MPH rats displaying less locomotor activity at the beginning of the test (Figure 1B; 15, 20, 25, and 35 min, p < .05). These results confirm previous work (
Discussion
Repeated exposure to MPH in early life affects a variety of behavioral and physiological responses in adulthood (Achat-Mendes et al 2003, Adriani et al 2005, Andersen et al 2002, Bolanos et al 2003, Carlezon et al 2003, Mague et al 2005). Given the impact of psychostimulants on brain reward circuitry (Nestler 2005, Nestler and Malenka 2004, Robinson 2004) and the decreased response to rewarding stimuli in adulthood seen after early MPH exposure (Carlezon et al 2003, Mague et al 2005), most
References (106)
- et al.
Symptomatic improvement in children with ADHD treated with long-term methylphenidate and multimodal psychosocial treatment
J Am Acad Child Adolesc Psychiatry
(2004) - et al.
Methylphenidate and MDMA adolescent exposure in mice: Long-lasting consequences on cocaine-induced reward and psychomotor stimulation in adulthood
Neuropharmacology
(2003) Emerging principles of intrinsic hippocampal organization
Curr Opin Neurobiol
(1993)- et al.
Spatial learning affects immature granule cell survival in adult rat dentate gyrus
Neurosci Lett
(2000) Stimulants and the developing brain
Trends Pharmacol Sci
(2005)- et al.
Altering the course of neurodevelopment: A framework for understanding the enduring effects of psychotropic drugs
Int J Dev Neurosci
(2004) - et al.
Stimulant treatment for children: A community perspective
J Am Acad Child Adolesc Psychiatry
(2000) - et al.
Restraint stress affects hippocampal cell proliferation differently in rats and mice
Neurosci Lett
(2004) - et al.
Regional dissociations within the hippocampus—memory and anxiety
Neurosci Biobehav Rev
(2004) - et al.
Methylphenidate treatment during pre- and periadolescence alters behavioral responses to emotional stimuli at adulthood
Biol Psychiatry
(2003)
Enhanced reactivity and vulnerability to cocaine following methylphenidate treatment in adolescent rats
Neuropsychopharmacology
Adolescent exposure to methylphenidate alters the activity of rat midbrain dopamine neurons
Biol Psychiatry
Adult neurogenesis is regulated by adrenal steroids in the dentate gyrus
Neuroscience
Adrenal steroid receptor immunoreactivity in cells born in the adult rat dentate gyrus
Brain Res
The many faces of CREB
Trends Neurosci
Understanding the neurobiological consequences of early exposure to psychotropic drugs: Linking behavior with molecules
Neuropharmacology
Enduring behavioral effects of early exposure to methylphenidate in rats
Biol Psychiatry
Methylphenidate differentially regulates c-fos and fosB expression in the developing rat striatum
Brain Res Dev Brain Res
Methylphenidate regulates c-fos and fosB expression in multiple regions of the immature rat brain
Brain Res Dev Brain Res
Chronic psychosocial stress and concomitant repetitive transcranial magnetic stimulation: Effects on stress hormone levels and adult hippocampal neurogenesis
Biol Psychiatry
Depression: A case of neuronal life and death?
Biol Psychiatry
Adult neurogenesis: Implications for psychiatry
Prog Brain Res
Hyperactivity following intradentate injection of colchicine: A role for dopamine systems in the nucleus accumbens
Pharmacol Biochem Behav
Actions of methylphenidate on dopaminergic neurons of the ventral midbrain
Biol Psychiatry
Differences in hippocampal mitotic activity within the dorsal and ventral hippocampus following flurothyl seizures in mice
Neurosci Lett
Stress and hippocampal neurogenesis
Biol Psychiatry
Dynamics of cell proliferation in the adult dentate gyrus of two inbred strains of mice
Brain Res Dev Brain Res
Prominent decline of newborn cell proliferation, differentiation, and apoptosis in the aging dentate gyrus, in absence of an age-related hypothalamus-pituitary-adrenal axis activation
Neurobiol Aging
Neurogenesis and depression: etiology or epiphenomenon?
Biol Psychiatry
Methylphenidate-induced plasticity: What should we be looking for?
Biol Psychiatry
Stress in early life inhibits neurogenesis in adulthood
Trends Neurosci
Milestones of neuronal development in the adult hippocampus
Trends Neurosci
Stress-induced decrease of granule cell proliferation in adult rat hippocampus: Assessment of granule cell proliferation using high doses of bromodeoxyuridine before and after restraint stress
Mol Cells
Stimulant actions in rodents: implications for attention-deficit/hyperactivity disorder treatment and potential substance abuse
Biol Psychiatry
Molecular heterogeneity along the dorsal-ventral axis of the murine hippocampal CA1 field: A microarray analysis of gene expression
Neuroscience
Early developmental exposure to methylphenidate reduces cocaine-induced potentiation of brain stimulation reward in rats
Biol Psychiatry
Activation of the retrohippocampal region in the rat causes dopamine release in the nucleus accumbens: Disruption by fornix section
Eur J Pharmacol
Neurobiology of depression
Neuron
National trends in the use of psychotropic medications by children
J Am Acad Child Adolesc Psychiatry
What are the long-term effects of methylphenidate treatment?
Biol Psychiatry
Adult neurogenesis: From precursors to network and physiology
Physiol Rev
Methylphenidate administration to adolescent rats determines plastic changes on reward-related behavior and striatal gene expression
Neuropsychopharmacology
Thyroid hormones affect neurogenesis in the dentate gyrus of adult rat
Neuroendocrinology
Altered responsiveness to cocaine in rats exposed to methylphenidate during development
Nat Neurosci
Production of new cells in the rat dentate gyrus over the lifespan: Relation to cognitive decline
Eur J Neurosci
Maternal care influences neuronal survival in the hippocampus of the rat
Eur J Neurosci
Hippocampal neurogenesis is not enhanced by lifelong reduction of glucocorticoid levels
Hippocampus
Regulation of adult neurogenesis by excitatory input and NMDA receptor activation in the dentate gyrus
J Neurosci
Adult neurogenesis produces a large pool of new granule cells in the dentate gyrus
J Comp Neurol
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2022, Pharmacology Biochemistry and BehaviorThe environmental sculpting hypothesis of juvenile and adult hippocampal neurogenesis
2021, Progress in NeurobiologyCitation Excerpt :Some theories propose that impaired neurogenesis leads to a disrupted capacity to distinguish safe from unsafe situations, which leads to overly generalized fears and impaired coping ability (Kheirbek et al., 2012). The sculpting hypothesis provides a novel perspective from which to view sensitive periods of vulnerability to factors that may disrupt neurogenesis, such as stress, inflammation, drugs and environmental exposures, as well as the time-course of when deficits would manifest (Dinel et al., 2014; Kozareva et al., 2019; Lagace et al., 2006; Loi et al., 2014; Snyder, 2019). Disruption of the sculpting process during the juvenile and adolescent periods would produce an adult dentate gyrus that is insufficiently specialized, mis-specialized or, potentially, over-specialized.