Repeated crack cocaine inhalation increases a panic-related response and alters serotonin immunoreactivity in the...

Crack cocaine is a highly addictive free base form of cocaine, that produces significant behavioral and neurobiological changes, including neuropsychiatric symptoms. Previously, we found that crack administration in rats altered escape responses and immunohistochemical activity in panic-modulating brain regions. This study investigates effects of crack cocaine using a rodent inhalation model. Male Wistar rats were divided into two groups and exposed to 100 or 250 mg of crack, for 5 days. On the fifth day, Group 1 was euthanized for plasma concentration of cocaine and metabolites. Animals from Group 2 were tested in the elevated T-maze (ETM), for measurement of avoidance and escape responses, in clinical terms associated to generalized anxiety and panic disorder, respectively. Locomotor activity was also assessed. Since serotonin (5-HT) is one of the main neurotransmitters associated to anxiety/panic modulation and cocaine interferes with 5-HT neurotransmission, we also analyzed FosB/deltaFosB immunoreactivity in 5-HT dorsal raphe (DR) cells. Plasma concentrations of cocaine and metabolites confirmed the effectiveness of the procedure and showed that exposure to 250 mg induced higher concentrations of cocaine and benzoylecgonine. Exposure to crack 250 mg decreased escape latencies, a panicogenic-like effect, and increased FosB/deltaFosB immunoreactivity in the lateral wings (lwDR) and dorsal region (DRD) of the DR. Double immunoreactivity was also increased in the DRD. lwDR 5-HT neurons were less activated. No other significant results were found. These observations contribute to a better understanding of behavioral and neurobiological effects of crack cocaine.