Effects of ayahuasca on the development of ethanol-induced behavioral sensitization and on a post-sensitization treatment in mice

- Ayahuasca (Aya) did not exert effects on the spontaneous locomotor activity of mice.
- Aya prevented the development of ethanol(Eth)-induced behavioral sensitization (BS).
- At high doses, Aya also inhibited acute Eth-induced hyperlocomotion.
- An 8-day treatment with Aya in the open-field did not induce BS to this drug.
- Counter-sensitization with Aya blocked the reinstatement of Eth-induced BS.

BackgroundHallucinogenic drugs were used to treat alcoholic patients in the past, and recent developments in the study of hallucinogens led to a renewal of interest regarding the application of these drugs in the treatment of addiction. In this scenario, accumulating evidence suggests that the hallucinogenic brew ayahuasca (Aya) may have therapeutic effects on substance abuse problems.MethodsWe investigated the effects of Aya on spontaneous locomotor activity and ethanol(Eth)-induced hyperlocomotion and subsequent locomotor sensitization by a two-injection protocol. Additionally, we tested the effect of Aya on an 8-day counter-sensitization protocol to modify sensitized responses induced by a repeated treatment with Eth (1.8 g/kg) for 8 alternate days.ResultsAya showed high sensitivity in preventing the development of Eth-induced behavioral sensitization, attenuating it at all doses (30, 100, 200, 300 or 500 mg/kg) without modifying spontaneous locomotor activity. At the highest doses (300 and 500 mg/kg), Aya also showed selectivity to both acute and sensitized Eth responses. Finally, a counter-sensitization strategy with 100 or 300 mg/kg of Aya for 8 consecutive days after the establishment of Eth-induced behavioral sensitization was effective in blocking its subsequent expression on an Eth challenge.ConclusionsWe demonstrated that Aya not only inhibits early behaviors associated with the initiation and development of Eth addiction, but also showed effectiveness in reversing long-term drug effects expression, inhibiting the reinstatement of Eth-induced behavioral sensitization when administered in the Eth-associated environment.