Glutamatergic contributions to nicotine-induced cognitive enhancement
Final Report Abstract
Our objectives for the supported project were to provide a better understanding of human amygdalahippocampal learning and to provide novel pharmacological avenues for cognitive enhancement. Our results give evidence for the enhancing effects of nicotine to declarative memory, as modeled by DCS and memantine. Metaplasticity control mechanisms may commence to function rapidly after their initial engagement to put hippocampal synapses and networks into a learning-sensitive state. Harnessing these mechanisms may prove to have important clinical advantages, particularly as the more tempting direct pharmacological manipulations of hippocampal plasticity are likely to be limited by severe side effects. Future studies will address the question of possible interactions between these neurotransmitters and provide new implications for the understanding of age-associated cognitive decline and new applications, such as potential augmentation to current therapies. Additional work addressed the effect of oxytocin to enhance social cognition. While we have identified the many and obvious links between preclinical findings and clinical studies suggesting a promising therapeutic potential for ocytocin treatments in psychiatric disorders, there is still need for more large-scale controlled clinical studies. Preliminary evidence showing that oxytocin might have a therapeutic potential in ameliorating at least some psychiatric disorders (e.g. autism) is nevertheless already encouraging. Continuing our work, it will be important to recognize that while increasing oxytocin concentrations in the brain may be an effective ‘kick-start’ method for improving psychosocial problems in psychiatric patients, it may primarily act as an indirect ‘facilitator’ of behavior through modulation of classical neurotransmitter signaling. It is likely, therefore, that its most effective therapeutic use will be in combination with other drugs or nonpharmacological treatments, particularly those such as cognitive behavioral therapy, that depend considerably on the quality of social interaction between therapist and patient.
Publications
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(2010). "Facilitation of learning by social-emotional feedback in humans is beta-noradrenergic-dependent." Neuropsychologia 48(10): 3168-3172
Mihov, Y., S. Mayer, et al.
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(2010). "Oxytocin enhances amygdala-dependent, socially reinforced learning and emotional empathy in humans." The Journal of Neuroscience 30: 4999-5007
Hurlemann, R., A. Patin, et al.
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(2010). "The N-Methyl-D-Aspartate Receptor Co-agonist D- Cycloserine Facilitates Declarative Learning and Hippocampal Activity in Humans." Biological Psychiatry 67(12): 1205-1211
Onur, O. A., T. E. Schlaepfer, et al.
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(2011). "Modulating amygdala responses to emotion: evidence from pharmacological fMRI." Neuropsychologia 49(4): 706-717
Patin, A. and R. Hurlemann
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(2011). "Noradrenergic-glucocorticoid modulation of emotional memory encoding in the human hippocampus." Psychol Med 41(10): 2167-2176
Kukolja, J., D. Klingmuller, et al.
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(2011). "Prosocial effects of oxytocin and clinical evidence for its therapeutic potential." Front Neuroendocrinol 32(4): 426-450
Striepens, N., K. M. Kendrick, et al.
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(2012). "Altered amygdala function in nicotine addiction: insights from human neuroimaging studies." Neuropsychologia 50(8): 1719-1729
Mihov, Y. and R. Hurlemann
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(2012). "Amygdala Lesion Profoundly Alters Altruistic Punishment." Biol Psychiatry 72(3): e5-e7
Scheele, D., Y. Mihov, et al.
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(2012). "Fear processing and social networking in the absence of a functional amygdala." Biol Psychiatry 72(1): 70-77
Becker, B., Y. Mihov, et al.
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(2012). "Overnight deprivation from smoking disrupts amygdala responses to fear." Hum Brain Mapp 33(6): 1407-1416
Onur, O. A., A. Patin, et al.
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(2012). "Oxytocin facilitates protective responses to aversive social stimuli in males." Proc Natl Acad Sci USA 109(44): 18144-18149
Striepens, N., D. Scheele, et al.
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(2012). "Oxytocin modulates social distance between males and females." J Neurosci 32(46): 16074-16079
Scheele, D., N. Striepens, et al.
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"Genetic variation in dopaminergic activity is associated with the risk for psychiatric side effects of levetiracetam." Epilepsia Vol 54 Issue 1, January 2013, Pages 36-44
Helmstaedter, C., Y. Mihov, M. R. Toliat, Holger Thiele, Peter Nuernberg, Susanne Schoch et al.
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"Mirroring Fear in the Absence of a Functional Amygdala." Biol Psychiatry April 1, 2013, Volume 73, Issue 7, Pages e9–e11
Mihov, Y., K. M. Kendrick, Benjamin Becker, Jacob Zschernack, Harald Reich et al.
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(2013). "A negative emotional and economic judgment bias in major depression." Eur Arch Psychiatry Clin Neurosci 5: 5
Scheele, D., Y. Mihov, et al.
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(2013). "Deciphering the neural signature of conversion blindness." Am J Psychiatry Volume 170 Issue 1, January 2013, Pages 121-122
Becker, B., D. Scheele, Rainald Moessner, Wolfgang Maier, and René Hurlemann
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(2013). "Nicotinic Acetylcholine Receptors Contribute to Learninginduced Metaplasticity in the Hippocampus." J Cogn Neurosci 7: 7
Becker, B., E. M. Klein, et al.
