Abstract

The goal of this study was to investigate the effects of acute cocaine injection or dopamine (DA) receptor antagonists on the medial prefrontal cortex (mPFC) gamma oscillations and their relationship to short term neuroadaptation that may mediate addiction. For this purpose, optogenetically evoked local field potentials (LFPs) in response to a brief 10 ms laser light pulse were recorded from 17 mice. D1-like receptor antagonist SCH 23390 or D2-like receptor antagonist sulpiride, or both, were administered either before or after cocaine. A Euclidian distance-based dendrogram classifier separated the 100 trials for each animal in disjoint clusters. When baseline and DA receptor antagonists trials were combined in a single trial, a minimum of 20% overlap occurred in some dendrogram clusters, which suggests a possible common, invariant, dynamic mechanism shared by both baseline and DA receptor antagonists data. The delay-embedding method of neural activity reconstruction was performed using the correlation time and mutual information to determine the lag/correlation time of LFPs and false nearest neighbors to determine the embedding dimension. We found that DA receptor antagonists applied before cocaine cancels out the effect of cocaine and leaves the lag time distributions at baseline values. On the other hand, cocaine applied after DA receptor antagonists shifts the lag time distributions to longer durations, i.e. increase the correlation time of LFPs. Fourier analysis showed that a reasonable accurate decomposition of the LFP data can be obtained with a relatively small (less than ten) Fourier coefficients.

Highlights

  • Use of psychostimulants, such as cocaine, is a serious health problem and opens the door to neurobiological changes in limbic and cortical circuits that engage cognitive and emotive processing

  • In this study we investigated changes in gamma oscillations following an acute administration of cocaine and the effects of selective dopamine (DA) receptor antagonist on the gamma band oscillations

  • The transient response contains information regarding the phase resetting of the entire local neural network, which has been successfully applied to epilepsy [139, 140] or Parkinson’s [141, 142] studies

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Summary

Introduction

Use of psychostimulants, such as cocaine, is a serious health problem and opens the door to neurobiological changes in limbic and cortical circuits that engage cognitive and emotive processing. We have just began to understand the cellular adaptations that occur in the cortex following a single exposure to cocaine and their contribution to the continuous and further use of drugs of abuse. The behavioral consequences of first time cocaine use are varied and appear. Dopamine receptor antagonists effects on neural activity decision to publish, or preparation of the manuscript

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