Abstract
196
Objectives Dopamine D2 receptors (D2R) are involved with wakefulness and we had shown that in controls sleep deprivation (SD) reduced striatal D2R availability but could not determine if this reflected dopamine increases or receptor downregulation. To evaluate this we compared dopamine increases induced by methylphenidate (MP) during SD and after rested wakefulness (RW) and reasoned that since MP blocks dopamine transporters, its dopamine enhancing effects would be greater, if indeed, dopamine was increased with SD.
Methods We scanned 20 controls with [11C]raclopride after placebo and after MP (40 mg po), after RW and after one night of SD. Non-specific binding potential (BPND) was used to quantify D2R availability.
Results BPND in ventral striatum (VS) was decreased by SD (2.80 ±.37) as compared to RW (2.95 ±.37; p<0.05) and correlated with decreased alertness (r=-0.44, p<0.05) and increased sleepiness (r=-0.50, p<0.03) with SD. However, MP-induced dopamine increases (measured as % decreases in BPND from placebo) in striatum did not differ between RW (6.9%) and SD (7.3%). SPM analysis corroborated the findings of D2R decreases in VS with SD and of equivalent MP-induced DA increases with SD and RW. Parallel microdialysis experiments in rodents showed no changes in baseline dopamine levels in ventral striatum nor in DA increases with MP after SD (24 hours).
Conclusions These findings are consistent with a downregulation of D2R in VS with SD that may contribute to the decreases in wakefulness that occur with SD.
Research Support Research supported by NIH’s Intramural Research Program (NIAAA) and by DOE (DE-AC01-76CH00016)