Crack cocaine inhalation increases seizure susceptibility by reducing acetylcholinesterase activity.

Crack cocaine is a highly addictive and potent stimulant drug. Animal studies have shown that the cholinergic system plays a role in neurotoxicity induced by cocaine or its active metabolites inhalation. Behavioral alterations associated with crack cocaine use include hyperactivity, depressed mood, and decreased seizure threshold. Here we evaluate the acetylcholinesterase (AChE) and reactive oxygen species (ROS) activity, behavioral profile, and the threshold for epileptic seizures in rats that received intrahippocampal pilocarpine (H-PILO) followed by exposure to crack cocaine (H-PILO + CRACK). Animals exposed to H-PILO + CRACK demonstrated increased severity and frequency of limbic seizures. The AChE activity was reduced in the groups exposed to crack cocaine alone (CRACK) and H-PILO + CRACK, whereas levels of ROS remained unchanged. In addition, crack cocaine exposure increased vertical locomotor activity, without changing water and sucrose intake. Short-term memory consolidation remained unchanged after H-PILO, H-PILO + CRACK, and CRACK administration. Overall, our data suggest that crack cocaine inhalation reduced the threshold for epileptic seizures in rats submitted to low doses of pilocarpine through the inhibition of AChE. Taken together, our findings can be useful in the development of effective strategies for preventing and treating the harmful effects of cocaine and crack cocaine on the central nervous system.

Maternal crack cocaine use in rats leads to depressive- and anxiety-like behavior, memory impairment, and increased seizure susceptibility in the offspring.

Crack users suffer the effects of cocaine present in the drug and the action of other active compounds from its pyrolysis. An emergent fact is an increase in the number of pregnant crack cocaine users. Studies suggest that crack cocaine and its metabolites cross the placenta, promoting premature birth, fever, irritability, sweating, and seizures in the early months of life. In children, the effects of crack cocaine have been associated with cognitive deficits, difficulty in verbalization, aggressiveness, and depression, besides enhancing the susceptibility to epileptic seizures, including status epilepticus (SE) in adulthood. Therefore, we investigated the effect of maternal exposure to smoke crack cocaine on several behavioral parameters in the offspring during adulthood. A series of behavioral tests and intrahippocampal pilocarpine (H-PILO) microinjection at sub-convulsive and convulsive doses in a rat model demonstrated that exposure to crack cocaine during the embryonic period leads to anxiogenic-like behavior and long-term memory impairment in both genders and promotes depressive-like behavior in the female. Besides, crack cocaine offspring exposed to a sub-convulsive H-PILO dose showed higher susceptibility to SE, increased seizure frequency, and neurodegeneration, while animals that received a convulsive dose of H-PILO displayed no alteration in SE severity. Taken together, our data suggest that crack cocaine exposure during the gestational period leads to an increased predilection for anxiety and depression, long-term memory deficits, and reduction in the threshold for developing epileptic seizures associated with neuronal death, which predispose crack cocaine babies to develop neuropsychological disorders.