Hormonal, Neurochemical, and Behavioral Response to a Forced Swim Test in Adolescent Rats throughout Cocaine Withdrawal

The use of cocaine in adults has been linked to depression and/or anxiety. Several studies have shown an association between cocaine-primed craving and depressive symptoms. In animal models, the forced swim test (FST) is frequently used for screening depressive-like behavior. This study aimed to verify the presence of depression-like symptoms in adolescent rats after chronic cocaine exposure by analyzing behavior in a FST: The subsequent alterations in neurotransmitters and hypothalamus-pituitary-adrenal axis activity induced by this test were also analyzed. Both male and female adolescent Wistar rats were submitted to a chronic "binge" pattern of administration of cocaine hydrochloride, and subjects were tested in a forced swim test 2 days after cocaine's last administration. At the end of the behavioral test, trunk blood was collected for quantification of corticosterone plasma levels, and hypothalamus, prefrontal cortex, amygdala, and hippocampus were dissected for neurochemical determinations. No significant differences were found in the behavior on the FST of both males and females after withdrawal from chronic cocaine administration. Nevertheless, plasma levels of corticosterone were increased in cocaine-treated males, although not significantly (P = 0.065). In females cocaine failed to affect corticosterone levels. Of interest, neurochemical analyses showed that dopamine turnover was decreased in amygdala in cocaine-treated males (not significantly, P = 0.055). No significant differences were found on neurotransmitter levels in the other brain regions analyzed. Withdrawal from chronic cocaine administration during adolescence did not have a significant effect on stress-induced behavioral alterations, although the neurochemical response to the stressful situation provided by FTS seemed to be affected.