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Many important physiological, behavioral, and psychoemotional effects of intravenous (IV) cocaine (COC) are too fast and transient compared with pharmacokinetic predictions, suggesting a possible involvement of peripheral neural mechanisms in their triggering. In the present study, we examined changes in cortical electroencephalogram (EEG) and neck electromyogram (EMG) induced in freely moving rats by IV COC administration at low, reinforcing doses (0.25-1.0 mg/kg) and compared them with those induced by an auditory stimulus and IV COC methiodide, which cannot cross the blood-brain barrier. We found that COC induces rapid, strong, and prolonged EEG desynchronization, associated with decrease in alpha and increase in beta and gamma activities, and EMG activation and that both begin within 2-6 s following the start of a 10-s injection; immediate components of this effect were dose independent. The rapid COC-induced changes in EEG and EMG resembled those induced by an auditory stimulus; the latter effects had shorter onset latencies and durations and were fully blocked during urethane anesthesia. Although urethane anesthesia completely blocked COC-induced EMG activation and rapid components of EEG response, COC still induced EEG desynchronization that was much weaker, greatly delayed (approximately 60 s), and associated with tonic decreases in delta and increases in alpha, beta, and gamma activities. Surprisingly, IV saline delivered during slow-wave sleep (but not quite wakefulness) also induced a transient EEG desynchronization but without changes in EMG activity; these effects were also fully blocked during anesthesia. Peripherally acting COC methiodide fully mimicked rapid EEG and EMG effects of regular COC, but the effects at an equimolar dose were less prolonged than those with regular COC. These data suggest that in awake animals IV COC, like somato-sensory stimuli, induces cortical activation and a subsequent motor response via its action on peripheral neural elements and involving rapid neural transmission. By providing a rapid neural signal and triggering transient 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.

american journal of physiology. regulatory, integrative and comparative physiology/american journal of physiology. regulatory, integrative, and comparative physiology

Rapid EEG desynchronization and EMG activation induced by intravenous cocaine in freely moving rats: a peripheral, nondopamine neural triggering