Drugs of Abuse Can Entrain Circadian Rhythms

Abstract

Circadian rhythms prepare organisms for predictable events during the Earth's 24-h day. These rhythms are entrained by a variety of stimuli. Light is the most ubiquitous and best known zeitgeber, but a number of others have been identified, including food, social cues, locomotor activity, and, most recently drugs of abuse. Given the diversity of zeitgebers, it is probably not surprising that genes capable of clock functions are located throughout almost all organs and tissues. Recent evidence suggests that drugs of abuse can directly entrain some circadian rhythms. We have report here that entrainment by drugs of abuse is independent of the suprachiasmatic nucleus and the light/dark cycle, is not dependent on direct locomotor stimulation, and is shared by a variety of classes of drugs of abuse. We suggest that drug-entrained rhythms reflect variations in underlying neurophysiological states. This could be the basis for known daily variations in drug metabolism, tolerance, and sensitivity to drug reward. These rhythms could also take the form of daily periods of increased motivation to seek and take drugs, and thus contribute to abuse, addiction and relapse.

The Role of Clock in Ethanol-Related Behaviors

“…Physiological, behavioral, and molecular rhythms are all affected by rewarding stimuli, including drugs of abuse and food. Rodent studies have shown that prolonged alcohol treatments can disrupt the circadian pattern of a variety of hormonal and behavioral rhythms (Kakihana and Moore, 1976;Kosobud et al, 2007, Madeira et al, 1997Rajakrishnan et al, 1999;Rosenwasser et al, 2005;Spanagel et al, 2005a). However, the molecular mechanisms of these disruptions are yet to be determined.…”

The effects of chronic marijuana use on circadian entrainment

“…Earlier studies exploring circadian rhythms and human drug addiction suggest chronic drug use commonly results in severe circadian alterations, not entrainment (see review in Hasler et al (2012) and Wasielewski & Holloway (2001)). However, other animal studies indicate psychoactive drugs of abuse (cocaine, methamphetamine, fluoxetine, nicotine, alcohol) can assist in entraining SCN-independent pacemakers (Kosobud et al, 2007;Manev & Uz, 2006). These SCN-independent pacemakers have been located in the parietal cortex, nucleus accumbens and caudate putamen, all areas of the brain also affected by cannabinoids (Akhisaroglu et al, 2004;Brievogel & Childers, 1998;Falcón & McClung, 2009;Masubuchi et al, 2000).…”

“…For instance, alcohol and psychostimulants, like cocaine, nicotine and amphetamines, have all demonstrated circadian sensitivity (Falcón & McClung, 2009;Iijima et al, 2002;Kosobud et al, 2007;McClung, 2007). Specifically, rodents are inclined to seek and prefer alcohol and stimulants at particular hours and are physiologically more responsive to these substances at specific times throughout the 24-h day (see review in Kosobud et al (2007)). Further, Falcón & McClung (2009) demonstrated stimulants and alcohol have similar interactions with the circadian timing mechanism and individuals dependent on these substances have alterations in their activity cycle, sleep/wake cycle and body temperature.…”

“…In mice models, researchers have determined that cannabinoids may alter the ability of the SCN to entrain to environmental light cues, specifically by modulating the release of gamma amino butyric acid (GABA) (Acuna-Goycolea et al, 2010). Unfortunately, to our knowledge, no literature has investigated behavioral consequences of circadian dysfunction and chronic marijuana use; however, it is known that other drugs of abuse alter and disrupt circadian rhythms (see review in Hasler et al (2012)), leading to detrimental outcomes on sleep, hormone regulation, blood pressure and eating habits (Iijima et al, 2002;Kosobud et al, 2007;Marchant & Mistleberger, 1997;McClung, 2007). For instance, alcohol and psychostimulants, like cocaine, nicotine and amphetamines, have all demonstrated circadian sensitivity (Falcón & McClung, 2009;Iijima et al, 2002;Kosobud et al, 2007;McClung, 2007).…”

“…Unfortunately, to our knowledge, no literature has investigated behavioral consequences of circadian dysfunction and chronic marijuana use; however, it is known that other drugs of abuse alter and disrupt circadian rhythms (see review in Hasler et al (2012)), leading to detrimental outcomes on sleep, hormone regulation, blood pressure and eating habits (Iijima et al, 2002;Kosobud et al, 2007;Marchant & Mistleberger, 1997;McClung, 2007). For instance, alcohol and psychostimulants, like cocaine, nicotine and amphetamines, have all demonstrated circadian sensitivity (Falcón & McClung, 2009;Iijima et al, 2002;Kosobud et al, 2007;McClung, 2007). Specifically, rodents are inclined to seek and prefer alcohol and stimulants at particular hours and are physiologically more responsive to these substances at specific times throughout the 24-h day (see review in Kosobud et al (2007)).…”