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Lasting aversive consequences of a single dose of 4-hydroxytamoxifen

Preprint Created on 22 Sep 2026 bioRxiv

4-hydroxytamoxifen (4-OHT) is commonly used to facilitate activity-dependent recombination in neurons. Here we show that one dose of 4-OHT devalues alcohol, contexts, and tastants, indicating that experimental designs using 4-OHT should control for its aversiveness. Further, reactivation of 4-OHT-responsive neurons causes conditioned taste avoidance. An activity screen coupled with graph theoretical analysis identifies candidate brain areas mediating these effects. We suggest these areas could be therapeutic targets for treating addiction.

Kyzar, E. J., Setara, R., Eisengart, M., Virkar, S., Rogerson, L., Ramirez, A., Salzman, C. D.

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