Cocaine Clause Samples

Cocaine. Cocaine was initially produced from the coca plant of South America, and in that form has been used as a stimulant for over 1000 years (reviewed in (▇▇▇▇▇▇▇▇ and ▇▇▇▇▇▇▇▇, 1989)). In the last 100 years, the active ingredient was isolated, synthesized, and while it was originally used as a supplement and a treatment for a variety of ailments, it is currently most often used illicitly as a recreational drug. The acute effects of cocaine on sleep are similar to those of amphetamine and include longer sleep latency, decreased total sleep time, and decreased REM (Boutrel and ▇▇▇▇, 2004; ▇▇▇▇▇▇▇▇▇▇▇▇ et al., 2008). Insomnia is a frequent adverse effect of cocaine. In addition, much like amphetamine, cocaine also increases locomotor activity in animal models. Abuse of cocaine in humans leads to sleep disturbances, most frequently fragmented sleep and alterations in REM (▇▇▇▇▇▇▇▇▇▇ and ▇▇▇▇▇, 2007). Even during abstinence from cocaine, some of these disturbances continue. However, modafinil is able to normalize sleep architecture and decrease daytime sleepiness in cocaine-dependent subjects (▇▇▇▇▇▇ et al., 2010). Modafinil has also been shown to be effective at reducing cocaine intake in cocaine-dependent individuals, and this may indicate that improving sleep quality is an important factor in that reduction (Dackis et al., 2005; ▇▇▇▇ et al., 2008). Cocaine acts by inhibiting the monoamine transporters, and thereby increasing extracellular concentrations of DA, NE, and 5-HT. All of these neurotransmitters are important for arousal, and their primary nuclei are parts of the ascending arousal pathway. The locomotor effects of cocaine seem primarily due to its inhibition of DAT. Cocaine-induced locomotor behavior is normal in NE transporter (NET) and SERT KO mice, but DAT KO mice are nonresponsive to acute cocaine (Hall et al., 2009). DAT KO mice also exhibit decreased self- administration of cocaine, indicating that DA is also responsible for at least some of the rewarding effects of this drug (▇▇▇▇▇▇▇ et al., 2009). However, while DAT blockers such as JHW007 can occlude the locomotor effects of cocaine (▇▇▇▇▇ et al., 2005), cocaine-induced locomotion is also significantly decreased in mice lacking the α1bAR (▇▇▇▇▇▇ et al., 2001). Furthermore, when pretreated with an α1AR antagonist, mice displayed decreased development and expression of cocaine sensitization (▇▇▇▇▇▇▇-▇▇▇▇▇▇ et al., 2006). In-depth studies of cocaine on sleep utilizing EEG monitoring have not been c...