Actions of Methylphenidate in the Hippocampus
August 18, 2015 at 12:32 AM | categories: hippocampus, mph
Contents
1 Actions of MPH in the Hippocampus
Most of our knowledge of the therapeutic effects of stimulants comes from studies focused on the prefrontal cortex and striatum, but there is increasing evidence of the relevance of catecholaminergic modulation in limbic regions such as the amygdala and hippocampus in mediating the motivation-enhancing effects of stimulant drugs [8, 12]. methylphenidate (MPH) increases hippocampal norepinephrine (NE) and dopamine (DA) in vivo [7, 11], both of which are known to affect plasticity such as long-term potentiation (LTP) and long-term depression (LTD) [1–5, 9, 10]. MPH enhances rat hippocampal NE to an extent comparable to that of striatal DA in microdialysis studies following i.p. injection [6]. Also, oral administration of a low dose of MPH preferentially enhances hippocampal NE efflux without affecting DA in the nucleus accumbens (NAcc) [7].
Acronyms
- DA
- dopamine
- LTD
- long-term depression
- LTP
- long-term potentiation
- MPH
- methylphenidate
- NAcc
- nucleus accumbens
- NE
- norepinephrine
References
[1] W. F. Hopkins and D. Johnston. Frequency-dependent noradrenergic modulation of long-term potentiation in the hippocampus. Science, 226 (4672):350–352, Oct 1984.
[2] S. E. Hyman, R. C. Malenka, and E. J. Nestler. Neural mechanisms of addiction: the role of reward-related learning and memory. Annu. Rev. Neurosci., 29:565–598, 2006.
[3] Y. Izumi, D. B. Clifford, and C. F. Zorumski. Norepinephrine reverses N-methyl-D-aspartate-mediated inhibition of long-term potentiation in rat hippocampal slices. Neurosci Lett, 142(2):163–166, Aug 1992.
[4] S. Jones and A. Bonci. Synaptic plasticity and drug addiction. Curr Opin Pharmacol, 5(1):20–25, Feb 2005.
[5] J. A. Kauer. Learning mechanisms in addiction: synaptic plasticity in the ventral tegmental area as a result of exposure to drugs of abuse. Annu. Rev. Physiol., 66:447–475, 2004.
[6] R. Kuczenski and D. S. Segal. Locomotor effects of acute and repeated threshold doses of amphetamine and methylphenidate: relative roles of dopamine and norepinephrine. J Pharmacol Exp Ther, 296(3):876–83, Mar 2001.
[7] R. Kuczenski and D. S. Segal. Exposure of adolescent rats to oral methylphenidate: preferential effects on extracellular norepinephrine and absence of sensitization and cross-sensitization to methamphetamine. J Neurosci, 22(16):7264–7271, Aug 2002. doi: 20026690. URL http://dx.doi.org/20026690.
[8] K. Lehmann, J. Lesting, D. Polascheck, and G. Teuchert-Noodt. Serotonin fibre densities in subcortical areas: differential effects of isolated rearing and methamphetamine. Brain Res Dev Brain Res, 147(1-2):143–52, Dec 2003.
[9] J. E. Lisman and A. A. Grace. The hippocampal-VTA loop: controlling the entry of information into long-term memory. Neuron, 46 (5):703–713, Jun 2005.
[10] M. J. Thomas, T. D. Moody, M. Makhinson, and T. J. O’Dell. Activity-dependent beta-adrenergic modulation of low frequency stimulation induced LTP in the hippocampal CA1 region. Neuron, 17(3): 475–482, Sep 1996.
[11] P. Weikop, T. Yoshitake, and J. Kehr. Differential effects of adjunctive methylphenidate and citalopram on extracellular levels of serotonin, noradrenaline and dopamine in the rat brain. European Neuropsychopharmacology, 17:658–671, 2007.
[12] T. E. Wilens, L. A. Adler, J. Adams, S. Sgambati, J. Rotrosen, R. Sawtelle, L. Utzinger, and S. Fusillo. Misuse and diversion of stimulants prescribed for ADHD: a systematic review of the literature. J Am Acad Child Adolesc Psychiatry, 47(1):21–31, Jan 2008.