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

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.

Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests

Objective: To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents. Methods: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors’ research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined. Results: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior. Conclusions: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.