Table 2.

Pharmacological interventions to tackle DS-associated cognitive deficits

Neurobiological Pathway	Pharmacological Compound	Cognitive Effect	References
SSRIs and mood stabilisers	Fluoxetine	Increases neurogenesis by enhancing proliferation and survival of neurons; restores 5-HT receptor and BDNF levels	Clark et al., 2006; Bianchi et al., 2010
	Lithium	Increases neurogenesis by restoring cell proliferation in subventricular zone	Bianchi et al., 2010
Neuroprotective peptides	NAPVSIPQ+SALLRSIPA	Protection from oxidative damage and apoptosis; prenatal treatment prevents developmental delays, glial deficits and aberrant ADNF expression	Brenneman et al., 2004; Busciglio et al., 2007; Toso et al., 2008
GABAA antagonists	Pentylenetetrazol	Improves hippocampal-based learning in behavioural tasks and enhances LTP	Fernandez et al., 2007; Rueda et al., 2008
	Picrotoxin	Improves hippocampal-based learning in behavioural tasks, enhances LTP and normalises NMDAR-mediated currents	Kleschevnikov et al., 2004; Fernandez et al., 2007
	α5IA	Improves hippocampal-based learning in behavioural tasks, normalises Sod1 overexpression and enhances learning-evoked immediate gene expression levels	Braudeau et al., 2001; Roche, 2011
NMDAR antagonists	Memantine	Improves hippocampal-based learning and fear conditioning in behavioural tasks, reduces excessive glutamate neurotransmission and increases BDNF levels	Costa et al., 206; Rueda et al., 2010; Lockrow et al., 2010; Mohan et al., 2009