Effects of acute caffeine on anxiety-related behavior in rats chronically exposed to the drug, with some evidence of possible withdrawal-reversal

Abstract

For 20days male and female PVG/c hooded rats were provided with caffeinated (approximately 50mg/kg/day) or unadulterated drinking water, and then their anxiety-related behavior was observed in an open field and elevated plus maze. Their choices of a brightness change were also observed in a Y maze to assess any caffeine effects on spatial memory. 24h later, all rats were tested again following an intraperitoneal injection of 50mg/kg acute caffeine, or vehicle. Earlier chronic caffeine decreased ambulation, walking, rearing, center occupancy and increased immobility in the open field thereby suggesting increased anxiety. However, occupancy of the plus-maze open arms and the Y-maze novel arm were increased by caffeine for male rats, but decreased for females probably because of sex differences in control levels of the response rather than to drug effects on anxiety and memory respectively. Following caffeine withdrawal, acute caffeine had the opposite effect to chronic treatment namely, increased open-field ambulation, walking, center occupancy and decreased immobility and defecation for caffeine-naïve rats that were suggestive of decreased anxiety. Similar but more consistent effects (plus decreased emergence latencies from a darkened start box into the open field) also typified the caffeine-experienced rats which in this case may have been accentuated by caffeine withdrawal-reversal. There was no evidence of either chronic or acute caffeine affecting spatial memory measured in the Y maze. There were also examples of lower overall activity and higher anxiety in male rats, than in females, and some sex-dependent caffeine effects.

Keywords: Anxiety; Chronic acute caffeine; Rats; Sex differences; Spatial memory; Withdrawal reversal.