Repeated crack cocaine administration alters panic-related responses and delta FosB immunoreactivity in panic-modulating brain regions

• DOI: 10.1007/s00221-020-06031-2
• Publication Date: 2021-02-11T12:13:28Z
• Authors: Barbara dos Anjos...; Maria de Fátima S...; Jéssica Alves Lemes; José Simões de An...; Regina Barbosa da...; Camilo Dias Seabr...; Daniel Araki Ribeiro; Milena de Barros ...
• Keywords: Dorsal Raphe Nucleus; Anxiety; Rats; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Escape Reaction; Animals; Crack Cocaine; Rats, Wistar; Maze Learning; Proto-Oncogene Proteins c-fos

Crack cocaine is the crystal form of cocaine, produced by adding sodium bicarbonate to cocaine base paste. Brazil is the largest consumer of crack cocaine in the world. Users of crack cocaine show important physiological and behavioral alterations, including neuropsychiatric symptoms, such as anxiety-related symptoms. Nevertheless, few pre-clinical studies have been previously performed to understand the neurobiological effects of crack cocaine. The purpose of the present study was to investigate effects of the subchronic treatment (5 days, IP) of rats with crack cocaine in an animal model of anxiety/panic, the elevated T-maze (ETM). The ETM model allows the measurement of two behavioral defensive responses, avoidance and escape, in clinical terms, respectively, associated to generalized anxiety and panic disorder, the two main psychiatric conditions that accompany substance use disorders. Immediately after the ETM model, animals were tested in an open field for locomotor activity assessment. Analysis of delta FosB protein immunoreactivity was used to map areas activated by crack cocaine exposure. Results showed that crack treatment selectively altered escape displayed by rats in the ETM test, inducing either a panicolytic (18 mg/kg IP) or a panicogenic-like effect (25 and 36 mg/kg IP). These effects were followed by the altered functioning of panic-modulating brain regions, i.e., the periaqueductal gray and the dorsal region and lateral wings of the dorsal raphe nucleus. Treatment with 36 mg/kg of crack cocaine also increased locomotor activity. These are the first observations performed with crack cocaine in a rodent model of anxiety/panic and contribute to a better understanding of the behavioral and neurobiological effects of crack cocaine.