Olanzapine Causes a Leptin-Dependent Increase in Acetylcholine Release in Mouse Prefrontal Cortex

Abstract

Replacing leptin by systemic administration restored the olanzapine-induced enhancement of ACh release in the prefrontal cortex of leptin-deficient mouse.

Neurotransmitter networks in mouse prefrontal cortex are reconfigured by isoflurane anesthesia

“…During in vivo neurochemical sampling, it is critically important to distinguish drug-induced declines in measured analytes from declines in measures that may reflect decreasing dialysis probe recovery, decreasing detector sensitivity, or some unidentified confound. As with previous neurochemical studies in mice (Gettys et al 2013;Van Dort et al 2009;Wathen et al 2012), changes in neurotransmitter concentrations over time were evaluated by comparing the slopes of each neurotransmitter time course during wakefulness and during isoflurane anesthesia. Figure 3 plots Ϫ1.532.…”

“…Surgical implantation of guide tubes for microdialysis. Humane procedures for implantation of intracranial guide tubes, placement of microdialysis probes, and in vivo microdialysis (Coleman et al 2006;Van Dort et al 2009;Wathen et al 2012) have been described in detail and are outlined below. All anesthetic inductions used loss of righting response as a surrogate measure for loss of consciousness (Vanini et al 2014).…”

“…Post hoc evaluation of differences in neurotransmitter concentrations during wakefulness vs. isoflurane anesthesia was provided by Fisher's least significant difference test. Sample sizes were based on previously published, in vivo microdialysis studies of neurotransmitters (Coleman et al 2006;DeMarco et al 2004;Douglas et al 2001Douglas et al , 2002Flint et al 2010;Gettys et al 2013;Van Dort et al 2009;Wathen et al 2012) and metabolomics (Bourdon et al 2018) in B6 mouse. Changes in neurotransmitter concentrations over time were evaluated for each of the eight transmitters by comparing the slopes across the wakefulness sampling period with slopes across the isoflurane sampling period.…”

Neuropharmacology of Sleep and Wakefulness

“…When dialyzed into the prefrontal cortex of mouse, the atypical antipsychotic olanzapine increases acetylcholine release in the prefrontal cortex. 198 The increase in acetylcholine release is significantly greater in C57BL/6J mice than in leptin-deficient mice. However, when leptin is restored to leptin-deficient mice, the olanzapine-induced increase in acetylcholine release is the same as that in the C57BL/6J mouse (Figure 4).…”

“…This suggests that leptin modulates the release of ACh within the prefrontal cortex and may also play a role in the cortical activation that occurs during wakefulness and REM sleep. Data reprinted from Wathen et al, 2012 198 with permission.…”