Differential Effects of Cocaine on Dopamine Neuron Firing in Awake and Anesthetized Rats
Authors:
- 1 February 2012
- journal article
- Published by Springer Nature in Neuropsychopharmacology
- Vol. 37 (7) , 1559-1571
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.Keywords
This publication has 118 references indexed in Scilit:
- Projection-Specific Modulation of Dopamine Neuron Synapses by Aversive and Rewarding StimuliNeuron, 2011
- Firing properties and functional connectivity of substantia nigra pars compacta neurones recorded with a multi-electrode arrayin vitroThe Journal of Physiology, 2010
- Low and high cocaine locomotor responding male Sprague–Dawley rats differ in rapid cocaine-induced regulation of striatal dopamine transporter functionNeuropharmacology, 2010
- Low or High Cocaine Responding Rats Differ in Striatal Extracellular Dopamine Levels and Dopamine Transporter NumberThe Journal of Pharmacology and Experimental Therapeutics, 2009
- Individual Differences in Dopamine Cell Neuroadaptations Following Cocaine Self-AdministrationBiological Psychiatry, 2009
- Cocaine disinhibits dopamine neurons in the ventral tegmental area via use‐dependent blockade of GABA neuron voltage‐sensitive sodium channelsEuropean Journal of Neuroscience, 2008
- Prominent Activation of Brainstem and Pallidal Afferents of the Ventral Tegmental Area by CocaineNeuropsychopharmacology, 2007
- Dopamine reward circuitry: Two projection systems from the ventral midbrain to the nucleus accumbens–olfactory tubercle complexBrain Research Reviews, 2007
- Glutamatergic Afferents of the Ventral Tegmental Area in the RatThe Journal of Neuroscience, 2007
- Low and high locomotor responsiveness to cocaine predicts intravenous cocaine conditioned place preference in male Sprague–Dawley ratsPharmacology Biochemistry and Behavior, 2007