Characterization of atypical antipsychotic drugs by a late decrease of striatal alpha1 spectral power in the electropharmacogram of freely moving rats

Abstract

Background and purpose: Drug administration modifies the balance of neurotransmitter-controlled ion channel activity and consequently the firing pattern of local neuronal populations and intracerebral field potentials. Fast Fourier Transformation of these field potentials provides an electropharmacogram depicting drug-induced changes within defined frequency ranges. The present investigation was undertaken to investigate the difference between atypical and typical antipsychotic drugs. Experimental approach: Adult Fisher rats were implanted with 4 bipolar concentric steel electrodes using a stereotactic surgical procedure. Field potentials from four selected brain areas in freely moving rats were used to analyse the frequency content of the electropharmacogram after administration of 4 clinically used atypical antipsychotic drugs. Key results: Atypical antipsychotics exerted effects similar to those reported for typical antipsychotics, on the electropharmacogram during the first hour after administration, whereas clear differences emerged during the second and third hour after dosing. During the latter period, only atypical antipsychotic drugs produced a statistically significant decrease in alpha1 and beta1 spectral power, especially within the striatum, somewhat less in the cortex. Conclusions and implications: Previous studies have attributed alpha1 frequency changes to the influence of 5-hydroxytryptamine (5-HT) and the present data are consistent with additional binding of atypical drugs to 5-HT receptors. This implies that a change in the balance between dopaminergic and 5-hydroxytryptaminergic neurotransmission (activation of both) is likely to underlie the relative lack of extrapyramidal side effects characteristic of atypical antipsychotics and also for their higher efficacy in the treatment of mood and cognition deficits in schizophrenics.

State-dependent alterations in sleep/wake architecture elicited by the M4 PAM VU0467154 – Relation to antipsychotic-like drug effects

“…However, the effects of clozapine and other APDs on sleep do not substantially improve cognition (Barch and Ceaser, 2012; Nuechterlein et al, 2004), perhaps due to residual sedative effects during wake. Daytime drowsiness or decreased arousal is common following APD administration in healthy humans, schizophrenia patients, and in healthy rats (Ahnaou et al, 2003; Czobor and Volavka, 1993; Dimpfel, 2007; Hughes et al, 1999; Roubicek and Major, 1977; Wichniak et al, 2006; Yoshimura et al, 2007). In the present studies, VU0467154 altered sleep in a manner similar to clozapine, suggesting potential APD-like activity on sleep architecture, but lacked the sedative profile of clozapine during waking periods.…”

Modulation of mGlu2 Receptors, but Not PDE10A Inhibition Normalizes Pharmacologically-Induced Deviance in Auditory Evoked Potentials and Oscillations in Conscious Rats

“…Hallucinogenic drugs such as lysergic acid diethylamide (LSD) and the serotonergic phenethylamine hallucinogen [–]-2,5-dimethoxy-4-methylamphetamine (DOM) increased the power in the alpha frequency oscillations [ 64 ]. The atypical antipsychotics decreased high frequency as well as slow alpha oscillations in humans and animals [ 65 – 68 ]. Amphetamine is widely used to recreate positive symptoms of schizophrenia in rodents, and this drug increases motor activity, during which the firing rate of neurons in the hippocampus rhythmically increased and decreased at ~8 Hz “theta rhythm” [ 69 ].…”

EnkephaloVision: Anatomical Functionality Indicated by Ultrashort Transient Regional EEG Spectral Power Changes during Cognitive and Emotional Challenges

“…An increase of power was only observed at the lateral frontal electrode positions. Alpha1 waves are related to serotonergic transmission [18]. Otherwise, always either no effect or an attenuation was seen with respect to all other electrode positions.…”