Morphine administration and abrupt cessation alter the behavioral diurnal activity pattern

Abstract

In mammals, there is an underlying mechanism that dictates the organism’s biological functions and daily activity schedule, known as circadian rhythms, which play a major role in maintaining steady metabolism, homeostasis, and immunity. Limited research has been done investigating the effects of continuous opiate administration on the circadian rhythm activity pattern. A change in circadian activity pattern is suggested as an experimental model to demonstrate long-term effect of the drug. The objective of this study was to investigate the effects of morphine treatment on the long term activity (24 hour) of the animal as well as the activity after abrupt removal. Since prescribed medication containing morphine is widely use and abused and its long term effects are not known. Male Sprague-Dawley rats were contained in stable conditions with a standard light/dark cycle recordings were taken before, during and after morphine pellet implantation. Cosinor analysis was used to fit a 24-hour curve to the activity pattern. Results indicate that morphine pellet administration alters the mesor, amplitude, the day-time and night-time activity levels, and during the withdrawal period demonstrates a remarkable change in the maximal circadian rhythm timing. The question whether morphine changes the circadian rhythm or a change in circadian rhythm results in tolerance and withdrawal is discussed.

Behavioral daily rhythmic activity pattern of adolescent female rat is modulated by acute and chronic cocaine

“…In animal models, the progressive augmentation of locomotor activity following repeated drug administration is considered the expression of behavioral sensitization to the drug, behavioral sensitization is one of the experimental marker indicator signs of drug dependence in animals (Askenasy et al 2007; Dafny and Yang 2006; Glaser et al 2012; Norrell et al 2010; Yang et al 2003, 2006, 2010, 2011). The neuroadaptation within the mesocorti-colimbic dopaminergic pathway, involving ventral teg-mental area, nucleus accumbens, and prefrontal cortex, is a major player in the development of behavioral sensitization (Chen et al 2009; Chong et al 2012; Claussen et al 2012; Claussen and Dafny 2012; Podet et al 2010; Salek et al 2012; Robinson and Becker 1986; Kalivas and Stewart 1991; Nestler 2002; Everitt and Robbins 2005; Kalivas and O’Brien 2008).…”

“…Psychostimulants such as methylphenidate were reported to exhibit an effect on the circadian activity pattern of locomotion (Algahim et al 2009, 2010; Antle et al 2012; Lee et al 2009, 2011). These changes in the circadian activity rhythm serves as an experimental marker in animals to correlate with the long-term effect of the drug (Algahim et al 2009, 2010, ; Bergheim et al 2012; Glaser et al 2012; Lee et al 2009, 2011; Norrell et al 2010). Many aspects of mammalian physiology operate on a diurnal or circadian rhythmic pattern that displays approximately 24 h cycle.…”

Melatonin in drug addiction and addiction management: Exploring an evolving multidimensional relationship

“…Also, sudden clearance or reduction in the plasma concentration of opioids of abuse results in withdrawal symptoms, including circadian rhythm disturbances like insomnia, jitteriness and restlessness[ 90 , 91 ]. Studies in animals have reported that chronic morphine administration resulted in a reduction in total activity within a 24 h period, and a dampening of the circadian amplitude in locomotor activity rhythm[ 92 , 93 ]. Abrupt withdrawal of morphine administration in rats has also been associated with sustained disruption of the circadian rhythms in locomotor activity, and alterations in plasma melatonin, β-endorphin, corticosterone, adenocorticothrophic hormone, and orexin concentrations[ 93 - 95 ].…”

“…Studies in animals have reported that chronic morphine administration resulted in a reduction in total activity within a 24 h period, and a dampening of the circadian amplitude in locomotor activity rhythm[ 92 , 93 ]. Abrupt withdrawal of morphine administration in rats has also been associated with sustained disruption of the circadian rhythms in locomotor activity, and alterations in plasma melatonin, β-endorphin, corticosterone, adenocorticothrophic hormone, and orexin concentrations[ 93 - 95 ]. Studies have also reported evidence of anxiety-related behaviour following cocaine withdrawal[ 96 ].…”

Adult female rats' altered diurnal locomotor activity pattern following chronic methylphenidate treatment

“…Disruption of circadian rhythm can result in short term conditions, such as jet lag, fatigue, insomnia, and contribute to long-term pathologies such as diabetes mellitus, heart disease, and hypertension (Bray and Young 2007, Filipski et al 2002, Karlsson et al 2001, Lamont et al 2007). In addition, changes in circadian rhythmic activity serve as experimental markers in animals to correlate with long-term effects of psychostimulant in humans (Algahim et al, 2009; Bergheim et al, 2012; Glaser et al, 2012; Lee et al 2011). …”