A exposição crônica à cafeína altera a resposta à nicotina durante a adolescência?: susceptibilidade à nicotina, comportamento e neuroquímica

Abstract

Caffeine and nicotine are on top of the list of psychoactive substances consumed in the world. Epidemiological data demonstrate the co-consumption and experimental studies support the idea of interactions between these drugs. Caffeine is consumed throughout life, while smoking usually starts during adolescence. The objective of this study was evaluate, during the adolescence of Swiss mice, the effects of the chronic exposure to caffeine on the susceptibility to nicotine (subproject 1), as well the effects of co-exposure on different behaviors (subproject 2). Caffeine exposure extended from the first day of mating until the last day of the behavioral tests. The animals were split into 3 experimental groups: CAF0.3 - free access to caffeine 0.3g/L as the only source of liquid (n=16 litters); CAF0.1 - free access to caffeine 0.1g/L as the only source of liquid (n=9 litters); control group (CONT) - free access to drinking water (n=15 litters). In subproject 1, on PN30, animals were tested in an open field (OF) or conditioned place preference (CPP) chamber. Nicotine (0,5mg/Kg, i.p.) or saline were administered immediately before the OF test. In the CPP, the animals associate the environment with the effects of nicotine (0,5mg/Kg, i.p.). Dopamine, the metabolic DOPAC, norepinephrine and turnover (DOPAC/dopamine) were quantified in the cerebral cortex through HPLC. In subproject 2, we only used CONT and CAF0.3 mice. On PN30, osmotic minipumps filled with nicotine (12mg/Kg/day) or saline were used, and the animals were co-exposed until PN45. Animals were tested either during co-exposure or after 5 days after the end of nicotine exposure. Mice were tested in the elevated plus maze (EPM) and OF on PN44 or PN49. Object recognition (OR) and forced swimming (FS) tests were run on PN45 and PN50. In subproject 1, nicotine increased locomotor activity in the OF, caffeine did not interfere with this result. Caffeine was anxiogenic at the higher dose but this effect was reversed by nicotine. In CPP, all groups were conditioned and caffeine failed to interfere with the effect of nicotine. Neither caffeine nor nicotine changed the concentrations of monoamines in the cerebral cortex. In subproject 2, during co-exposure, nicotine was anxiolytic in the EPM. Distinctively, during nicotine withdrawal, caffeine evoked an anxiolytic effect. Nicotine withdrawal evoked an increase in locomotor activity in CONT-NIC group, and a reduction in exploratory activity. In the OF, caffeine presented a reduction in locomotor activity and increased anxiety-like behavior both during co-exposure and during nicotine withdrawal. In the OR, CAF animals explored less the objects. In addition, nicotine evoked cognitive impairment was not identified in mice co-exposed to caffeine and nicotine. During nicotine withdrawal, this deficit was no longer identified. In the FS, nicotine evoked an anti-depressant effect. Distinctively, during nicotine withdrawal caffeine evoked an increase in depressive-like behavior. Altogether, these data show that chronic exposure to caffeine does not alter the susceptibility to nicotine during adolescence. Nevertheless, functional interactions between these drugs were identified in different behavioral tests used, requiring further studies to better understand the mechanisms that underlie these interactions.