Cocaine action on peripheral, non-monoamine neural substrates as a trigger of electroencephalographic desynchronization and electromyographic activation following i.v. administration in freely moving rats.
Many important physiological, behavioral and subjective effects of i.v. cocaine (COC) are exceptionally rapid and transient, suggesting a possible involvement of peripheral neural substrates in their triggering. In the present study, we used high-speed electroencephalographic (EEG) and electromyographic (EMG) recordings (4-s resolution) in freely moving rats to characterize the central electrophysiological effects of i.v. COC at low doses within a self-administration range (0.25-1.0 mg/kg). We found that COC induces rapid, strong, and prolonged desynchronization of cortical EEG (decrease in alpha and increase in beta and gamma activity) and activation of the neck EMG that begin within 2-6 s following the start of a 10-s injection; immediate components of both effects were dose-independent. The rapid effects of COC were mimicked by i.v. COC methiodide (COC-MET), a derivative that cannot cross the blood-brain barrier. At equimolar doses (0.33-1.33 mg/kg), COC-MET had equally fast and strong effects on EEG and EMG total powers, decreasing alpha and increasing beta and gamma activities. Rapid EEG desynchronization and EMG activation was also induced by i.v. procaine, a structurally similar, short-acting local anesthetic with virtually no effects on monoamine uptake; at equipotential doses (1.25-5.0 mg/kg), these effects were weaker and shorter in duration than those of COC. Surprisingly, i.v. saline injection delivered during slow-wave sleep (but not during quiet wakefulness) also induced a transient EEG desynchronization but without changes in EMG and motor activity; these effects were significantly weaker and much shorter than those induced by all tested drugs. These data suggest that in awake animals, i.v. COC induces rapid cortical activation and a subsequent motor response via its action on peripheral non-monoamine neural elements, involving neural transmission via visceral sensory pathways. By providing a rapid neural signal and triggering neural activation, such an action might play a crucial role in the sensory effects of COC, thus contributing to the learning and development of drug-taking behavior.
Behavioral Neuroscience Branch, National Institute on Drug Abuse, Intramural Research Program, National Institutes of Health, DHHS, Baltimore, MD 21224, USA.
M S
MS
Smirnov
E A
EA
Kiyatkin
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000502:physiology; D002491:Central Nervous System Agents / Q000008:administration & dosage / Q000494:pharmacology; D003042:Cocaine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology*; D003344:Cortical Synchronization / Q000187:drug effects*; D018765:Dopamine Uptake Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004569:Electroencephalography; D004576:Electromyography; D007275:Injections, Intravenous; D008297:Male; D009043:Motor Activity / Q000187:drug effects* / Q000502:physiology*; D009334:Neck Muscles / Q000187:drug effects / Q000294:innervation / Q000502:physiology; D010525:Peripheral Nerves / Q000187:drug effects* / Q000502:physiology; D011343:Procaine / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D020318:Rats, Long-Evans; D013997:Time Factors
D002491:Central Nervous System Agents; D018765:Dopamine Uptake Inhibitors; D011343:Procaine; C076070:cocaine methiodide; D003042:Cocaine