Sex-dependent modification by chronic caffeine of acute methamphetamine effects on anxiety-related behavior in rats.

For fourteen days, male and female PVG/c hooded rats were provided continuously with either pure drinking water, or water containing caffeine in a quantity approximating a daily dose of 31.1 mg/kg. Then at intervals of 3 days, they were administered 1, 2 mg/kg methamphetamine (MA) or saline before being tested for anxiety-related behavior in a zero maze or a light/dark box, or their short-term spatial memory was assessed in a Y maze following introduction of a novel brightness change in one of the arms. Each rat experienced each type of apparatus with the same acute MA or saline treatment while still exposed to chronic caffeine or pure drinking water. While chronic caffeine on its own did not affect any behavioral measure, acute MA was anxiolytic for male rats suggested by increased entries and occupancy of zero-maze enclosed areas, and decreased emergence latencies and increased entries into the light/dark-box light compartment. Females were less affected than males by MA in both types of apparatus unless they also consumed caffeine. For male rats, choices of the Y-maze novel arm were affected by neither caffeine nor MA, but for females provided with unadulterated water, such choices were reduced by 1 mg/kg MA but increased for those exposed to caffeine, thereby suggesting either impaired or improved memory respectively. However, changes in anxiety could also explain these results. Overall, results generated in the three types of apparatus supported potentiation by caffeine of any effects of MA on anxiety for females only.