RESUMEN
Caffeine is a common active adulterant found in illicit drugs of abuse, including coca paste (CP). CP is a smokable form of cocaine mainly consumed in South America, produced during the cocaine-extraction process. CP has high abuse liability and its chronic consumption induces severe sleep-wake alterations. However, the effect of CP on the sleep-wake cycle and the effect of the presence of caffeine as an adulterant remain unknown. We studied the effect of an acute intraperitoneal injection of 2.5 and 5 mg/kg of a representative CP sample adulterated with caffeine (CP1) on the rat sleep-wake cycle. Compared with saline, administration of CP1 induced an increase in wakefulness and a decrease in light (light sleep) and slow wave sleep that was larger than the effects produced by equivalent doses of cocaine. Compared with CP1, combined treatment with cocaine (5 mg/kg) and caffeine (2.5 mg/kg), a surrogate of CP1, elicited similar effects. In contrast, a nonadulterated CP sample (CP2) produced an effect that was not different from cocaine. Our data indicate that caffeine produces a significant potentiation of the wakefulness-promoting effect of cocaine, suggesting that caffeine should be explored as a causal agent of clinical symptoms observed in CP users.
Asunto(s)
Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Ritmo Circadiano/efectos de los fármacos , Coca , Cocaína/farmacología , Inhibidores de Captación de Dopamina/farmacología , Animales , Relación Dosis-Respuesta a Droga , Combinación de Medicamentos , Contaminación de Medicamentos , Masculino , Actividad Motora/efectos de los fármacos , Ratas , Ratas WistarRESUMEN
Recently, a novel type of fast cortical oscillatory activity that occurs between 110 and 160 Hz (high-frequency oscillations (HFO)) was described. HFO are modulated by the theta rhythm in hippocampus and neocortex during active wakefulness and REM sleep. As theta-HFO coupling increases during REM, a role for HFO in memory consolidation has been proposed. However, global properties such as the cortex-wide topographic distribution and the cortico-cortical coherence remain unknown. In this study, we recorded the electroencephalogram during sleep and wakefulness in the rat and analyzed the spatial extent of the HFO band power and coherence. We confirmed that the HFO amplitude is phase-locked to theta oscillations and is modified by behavioral states. During active wakefulness, HFO power was relatively higher in the neocortex and olfactory bulb compared to sleep. HFO power decreased during non-REM and had an intermediate level during REM sleep. Furthermore, coherence was larger during active wakefulness than non-REM, while REM showed a complex pattern in which coherence increased only in intra and decreased in inter-hemispheric combination of electrodes. This coherence pattern is different from gamma (30-100 Hz) coherence, which is reduced during REM sleep. This data show an important HFO cortico-cortical dialog during active wakefulness even when the level of theta comodulation is lower than in REM. In contrast, during REM, this dialog is highly modulated by theta and restricted to intra-hemispheric medial-posterior cortical regions. Further studies combining behavior, electrophysiology and new analytical tools are needed to plunge deeper into the functional significance of the HFO.
Asunto(s)
Corteza Cerebral/fisiología , Sueño/fisiología , Ritmo Teta/fisiología , Vigilia/fisiología , Animales , Electroencefalografía/métodos , Masculino , Ratas , Ratas WistarRESUMEN
Higher cognitive functions require the integration and coordination of large populations of neurons in cortical and subcortical regions. Oscillations in the high frequency band (30-100 Hz) of the electroencephalogram (EEG), that have been postulated to be a product of this interaction, are involved in the binding of spatially separated but temporally correlated neural events, which results in a unified perceptual experience. The extent of this functional connectivity can be examined by means of the mathematical algorithm called "coherence", which is correlated with the "strength" of functional interactions between cortical areas. As a continuation of previous studies in the cat [6,7], the present study was conducted to analyze EEG coherence in the gamma band of the rat during wakefulness (W), non-REM (NREM) sleep and REM sleep. Rats were implanted with electrodes in different cortical areas to record EEG activity, and the magnitude squared coherence values within the gamma frequency band of EEG (30-48 and 52-100 Hz) were determined. Coherence between all cortical regions in the low and high gamma frequency bands was greater during W compared with sleep. Remarkably, EEG coherence in the low and high gamma bands was smallest during REM sleep. We conclude that high frequency interactions between cortical areas are radically different during sleep and wakefulness in the rat. Since this feature is conserved in other mammals, including humans, we suggest that the uncoupling of gamma frequency activity during REM sleep is a defining trait of REM sleep in mammals.