Differential Effects of Cocaine on Dopamine Neuron Firing in Awake and Anesthetized Rats

Abstract

Cocaine (benzoylmethylecgonine), a natural alkaloid, is a powerful psychostimulant and a highly addictive drug. Unfortunately, the relationships between its behavioral and electrophysiological effects are not clear. We investigated the effects of cocaine on the firing of midbrain dopaminergic (DA) neurons, both in anesthetized and awake rats, using pre-implanted multielectrode arrays and a recently developed telemetric recording system. In anesthetized animals, cocaine (10 mg/kg, intraperitoneally) produced a general decrease of the firing rate and bursting of DA neurons, sometimes preceded by a transient increase in both parameters, as previously reported by others. In awake rats, however, injection of cocaine led to a very different pattern of changes in firing. A decrease in firing rate and bursting was observed in only 14% of DA neurons. Most of the other DA neurons underwent increases in firing rate and bursting: these changes were correlated with locomotor activity in 52% of the neurons, but were uncorrelated in 29% of them. Drug concentration measurements indicated that the observed differences between the two conditions did not have a pharmacokinetic origin. Taken together, our results demonstrate that cocaine injection differentially affects the electrical activity of DA neurons in awake and anesthetized states. The observed increases in neuronal activity may in part reflect the cocaine-induced synaptic potentiation found ex vivo in these neurons. Our observations also show that electrophysiological recordings in awake animals can uncover drug effects, which are masked by general anesthesia.

Activation of D2 autoreceptors alters cocaine-induced locomotion and slows down local field oscillations in the rat ventral tegmental area

“…36 adult male Wistar rats, weighing 250-300 grams, were implanted with a microelectrode array consisting of 8 platinum-iridium electrodes and designed so as to span the whole extent of the VTA (see details below and in Koulchitsky et al, 2012 Surgical and histological procedures were as described in detail elsewhere (Koulchitsky et al, 2012).…”

“…The recording site was then marked by an electrolytic lesion of the brain tissue through a previously implanted electrodes (1.0 mA cathodal current for 6 s), and animals were perfused intracardially with saline followed by a 4% formaldehyde saline solution. The brains were then removed and stored for histological examination (Koulchitsky et al, 2012).…”

“…its maximum at this time (Koulchitsky et al, 2012). Also, because preliminary experiments demonstrated that low-dose quinpirole alone strongly suppresses locomotion, this drug regimen was not investigated in this study.…”

“…Voluntary locomotion by itself is associated with changes in the firing rate of a majority of VTA DA neurons (Koulchitsky et al, 2012), and with modifications of the frequency of brain oscillations (Oddie and Bland, 1998;Orzel-Gryglewska et al, 2014;Vanderwolf, 1969). This created a problem for the direct comparison of LFP frequency spectra across different groups.…”

The Aversive Agent Lithium Chloride Suppresses Phasic Dopamine Release Through Central GLP-1 Receptors

“…Our work extends these findings to include a dopamine-suppressive action of an agent, LiCl, which produces a long-lasting aversive state Tomasiewicz et al, 2006). Dopamine neuron responses to stimuli can differ between anesthetized and awake subjects (Koulchitsky et al, 2012). We investigated the dopamine response to LiCl in both anesthetized and awake rats and consistently found that LiCl suppressed evoked dopamine release.…”