Adolescent Cocaine Residually Impairs Working Memory and Enhances Fear Memory in Rats

The residual effects of cocaine during adolescence on memory in male young adult rats were studied. Animals were injected with 20 mg/kg cocaine on postnatal Days 28 through 35, whereas lab-chow (LC) and pair-fed (PF) control subjects received saline. Assessment of spatial working and long-term memory in the Morris water maze, and 72-h retention of an inhibitory avoidance task was conducted at about 5 and 9 weeks postcocaine, respectively. Relative to PF control subjects, cocaine-treated subjects showed impairments in the water maze when required to swim to the hidden platform placed in a quadrant diagonal from the location of its original location (i.e., on reversal learning). These same drug-treated animals, however, exhibited enhanced inhibitory avoidance retention relative to both control groups. These seemingly disparate findings are seen as being consistent with previous data showing that cocaine during adolescence residually impairs spatial memory and leads to enhanced fear responses. Moreover, when taken with previous findings from our laboratory, the present water maze data indicate that the deleterious effects of cocaine, when administered during adolescence, is delayed until 5 weeks after initiation of abstinence. It is speculated that alterations to limbic circuitry, especially those associated with the amygdala, account for the behavioral results observed.