Ibogaine modulates cocaine responses which are altered due to environmental habituation: In vivo microvoltammetric and behavioral studies

Abstract

Ibogaine, a serotonergic (5-HTergic) indole alkaloid, was studied for cocaine modulatory effects on four parameters of behavior by computerized infrared photocell beam detection. The behavioral parameters were: a) locomotor activity (ambulations), b) rearing, c) stereotypy (fine movements, primarily grooming), and d) agoraphobia [(thigmotaxis) a natural tendency to avoid the center of the behavioral chamber]. With each behavioral data point, dopamine (DA) release, and serotonin (5-HT) release were detected within seconds in nucleus accumbens (NAcc) of the same behaving male Sprague-Dawley rats, using in vivo electrochemistry (voltammetry). Ibogaine was administered (40 mg/kg IP) for 4 consecutive days. Importantly, the DAergic and the 5-HTergic responses to (SC) cocaine and two behavioral responses, ambulations and central ambulations, were reduced in intensity due to extended time spent in the novel behavioral chamber (habituated). Rearing and fine movement patterns were not habituated. The results show that ibogaine downmodulated the (SC) cocaine-induced increase in NAcc DA release ( p < 0.0001) and potentiated the (SC) cocaine-induced decrease in NAcc 5-HT release ( p < 0.0001). Concurrently, ibogaine downmodulated cocaine-induced ambulation ( p < 0.0001) and central ambulation behavior ( p < 0.0001). On the other hand, the behavioral parameters that did not exhibit habituation, i.e., rearing behavior and fine movement behavior, were not downmodulated by ibogaine ( p < 0.1558) ( p < 0.3763), respectively. Furthermore, ibogaine itself did not significantly alter NAcc DA release over the 2-h period studied ( p < 0.9113) although individual time points were significantly affected bidirectionally. Concurrently ibogaine significantly increased 5-HT release ( p < 0.0155). Behaviorally, ibogaine appears to be a weak psychostimulant. The data show a critical modulatory role for 5-HT in ibogaine-cocaine interactions. Also elucidated as critical is the efficacy of ibogaine when the response to (SC) cocaine is decreased due to the habituation of the animals to their environment.