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

Abstract

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.

Critical Role of Peripheral Actions of Intravenous Nicotine in Mediating Its Central Effects

“…NIC Consistent with our previous work (Kiyatkin and Smirnov, 2010) and early observations in cats (Yamamoto and Domino, 1975), stress-and cue-free injection of pharmacologically neutral saline made during high-magnitude, lowfrequency sleep-like activity rapidly but transiently decreased cortical and VTA EEG total powers, with phasic decreases in a and phasic increases in b and g waves (see Figure 2). Although no visual behavioral responses typically occurred following saline injection, the effect on EMG was also significant, but much weaker than that seen with NIC or somato-sensory stimuli.…”

“…Consistent with this sensory mechanism, the pattern of EEG desynchronization induced by i.v. NIC resembled that seen with sensory stimuli (Kiyatkin and Smirnov, 2010), but the changes had definite onset latencies and were much stronger and more prolonged. Consistent with a well-known inhibiting action of general anesthesia on neural responses to somatosensory stimuli, we found that the initial components of EEG response to i.v.…”

“…NIC at low, human-relevant doses induces rapid, strong, and relatively prolonged EEG desynchronization, which appears within the duration of a 15-s injection (0-5 or 5-10 s) and peaks at about 15-25 s after its start. Similar to simple sensory stimuli such as sound (Kiyatkin and Smirnov, 2010), NIC in both structures induced a typical activation triad: decrease in a and increases in b and g activities, which all reached significance level at 5-10 s after the injection start. However, in contrast to simple sensory stimuli, NIC-induced changes in EEG were much stronger and longer lasting, especially with respect to high-frequency b and g activities.…”

“…Each rat was surgically prepared for chronic EEG and EMG as described previously in detail (Kiyatkin and Smirnov, 2010). Under general anesthesia (equithesin 0.33 ml/100 g i.p.…”

“…While there are numerous studies aimed to correlate EEG signals with specific neuronal activity and neural processes (see Hobson, 1999, Buzsaki, 2006, Steriade and McCarley, 2005, for review), EEG desynchronization is a valuable index of global neural activation. EEG desynchronization can result from either sensory input, appear 'spontaneously' in association with awakening and behavioral activity or be induced by pharmacological drugs (Kiyatkin and Smirnov, 2010;McClung et al, 1976McClung et al, -1977Sasaki et al, 1996). In addition, an event-related EEG desynchronization is typically tightly related to increased EMG activity that reflects alterations in tonic and phasic muscular activity, a centrally mediated peripheral response to the sensory signal.…”