MK-801 disrupts and nicotine augments 40 Hz auditory steady state responses in the auditory cortex of the urethane-anesthetized rat

Multisensory stimuli elicit altered oscillatory brain responses at gamma frequencies in patients with schizophrenia

“…A recent study by Tikka et al (2013) indicated increased gamma-band power in unmedicated patients with schizophrenia relative to controls; however, medication levels only corresponded to gamma-band power in one of the group clusters, suggesting that this alone cannot explain the current results. Finally, Sivarao et al (2013) reported that nicotine appears to enhance gamma-band power associated with the auditory steady-state response in rats. Nicotine is a known confound in the current study with decreased access to HC who smoke based on smoking cessation programs, thereby limiting the ability to match on this factor in large studies.…”

40 Hz Auditory Steady-State Response Is a Pharmacodynamic Biomarker for Cortical NMDA Receptors

“…It is therefore possible for acetylcholine, dopamine, or serotonin to play a mediatory role in ASSR PLF effects. Indeed, nicotinic cholinergic stimulation has been previously shown to augment 40 Hz ASSR power and PLF (Sivarao et al, 2013). Similarly, dopamine release-promoting agents like dexamphetamine have been shown to augment 40 Hz ASSR evoked power but not PLF (Albrecht et al, 2013).…”

“…This line of reasoning also presupposes that in the baseline condition, the evoked ASSR PLF is likely to be submaximal and that it can be increased by exogenous factors such as augmenting synaptic glutamate. This assumption seems reasonable as the NMDA receptors on PV+ neurons have been shown to be critical for entrainment at 40 Hz in empirical as well as modeling studies (Carlen et al, 2012;Kirli et al, 2014;Nakao and Nakazawa, 2014;Spencer, 2009), and because baseline 40 Hz ASSR can be improved by exogenous modulators like attention (Albrecht et al, 2013;Skosnik et al, 2007;Ross et al, 2004) or by pharmacological intervention that affect key neurotransmitters (Albrecht et al, 2013;Sivarao et al, 2013;Sullivan et al, 2015;Vohs et al, 2012). As the two intermediate doses of ketamine produced 34 and 62% of NMDA block while not significantly affecting ASSR PLF, we speculate that a baseline PLF response involves engagement of ∼ 38-66% of the available cortical NMDA receptors.…”

“…Taking advantage of this important validation, preclinical studies often employ a short-term disruption in NMDA neurotransmission to mimic a psychosis-like state (Adell et al, 2012;Frohlich and Van Horn, 2014;Gunduz-Bruce, 2009). Several groups have used this approach to understand the role of NMDA receptors in the 40 Hz ASSR (Sivarao et al, 2013;Sullivan et al, 2015;Vohs et al, 2012). Unfortunately, these studies reported opposite modulation of the ASSR signal with NMDA antagonists while employing divergent methodology.…”

“…Unfortunately, these studies reported opposite modulation of the ASSR signal with NMDA antagonists while employing divergent methodology. Sivarao et al (2013) showed that a low dose of the potent NMDA antagonist MK-801 attenuated ASSR at 40 Hz in anesthetized rats, Sullivan et al (2015) reported that a single dose of MK-801 increased phase locking at 40 Hz in awake behaving rats, whereas Vohs et al (2012) reported an increase in phase locking at multiple frequencies after a single dose of ketamine in conscious rats. Thus, anesthetized and awake rats produced opposite effects on 40 Hz ASSR following acute administration of an NMDA antagonist.…”