Circadian Rhythms of Dopamine and Cholecystokinin in Nucleus Accumbens and Striatum of Rats—Influence on Dopaminergic Stimulation

Abstract

The concentrations of cholecystokinin (CCK) and dopamine (DA) were determined in the nucleus accumbens (anterior, posterior) and striatum of rats every 2 h during a period of 24 h. For both substances, a circadian rhythm was found, which was best fitted by a dominant 24-h period superimposed by the second (12 h) and fourth (6 h) harmonics. The rhythms in CCK and DA were negatively correlated because of a difference in phase position by approximately 3 h. A dominant DA peak was found in the light phase coinciding with a trough in CCK and vice versa in the dark phase. Based on these data, CCK and DA were determined in rats treated with gamma-butyrolactone (GBL; inhibitor of DA release) or thyrotropin-releasing hormone (TRH; stimulator of DA release) at 0900 h or 1300 h to study a putative time-dependency in drug effects. After GBL treatment, CCK as well as DA increased by up to 200% whereas TRH administration led to a rather complex alteration, inasmuch as CCK was increased or decreased, depending on circadian time, whereas the rhythmic pattern in DA remained relatively unaffected. Comparing the drug effects obtained at 0900 h with the response seen at 1300 h revealed significant quantitative as well as qualitative differences. The results demonstrate that the neurotransmission system investigated changed its level of activity depending on time of day. No changes were obtained that convincingly may be ascribed to colocalization of DA and CCK. It is concluded that the chronobiological data indicate a close interaction of CCK and DA in various areas of the rat brain, independent of colocalization.

An important role for Cholecystokinin, a CLOCK target gene, in the development and treatment of manic-like behaviors

“…It is likely that CLOCK also contributes to the strong circadian rhythm in Cck expression. 34, 35 As expected by the sequence of the CLOCK∆19 protein, this protein can still bind to the Cck promoter but cannot activate transcription. We find that levels of H3K4me3, a histone modification associated with transcriptional activation, are decreased at the Cck promoter when compared to WT mice.…”

Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management

“…Previous studies have shown that plasma dopamine and its metabolites changes with circadian rhythm not only just in humans (Sowers and Vlachakis, 1984), but also in CSF in primate animals (Perlow et al, 1977) and in the striatum of rat (Schade et al, 1995; Castaneda et al, 2004). Another study indicated that the dopamine receptor responsiveness is modulated by the circadian rhythm at the level of spinal cord in decapitated Drosophila melanogaster (Andretic and Hirsh, 2000).…”

Photoperiodic suppression of drug reinstatement

“…Our laboratory and others have reported time-of-day differences in DAT and TH protein levels (Sleipness et al, 2007b, Webb et al, 2009a, Webb et al, 2009b) and in DAT function (Sleipness et al, 2008) in the mPFC and nucleus accumbens. Several other groups have also demonstrated diurnal or circadian changes in dopamine and its metabolites (O’Neill and Fillenz, 1985, Paulson and Robinson, 1994, Schade et al, 1995, Paulson and Robinson, 1996, Feenstra et al, 2000, Castaneda et al, 2004, Webb et al, 2009a) and in dopamine D2 receptor function (Tonissaar et al, 2006). However, as far as we know, the influence of altered photoperiod on DAT and TH within the mesocortical/mesolimbic DA system has not been examined.…”