Abstract
Rationale
Methamphetamine addiction is a persistent and intractable pathological learning and memory, whereas no approved therapeutics is available. However, few attentions have been paid to how associative learning participates in the formation of intractable memory related to drug addiction
Objectives and methods
To investigate the role of associative learning in methamphetamine addiction and the underlying neurobiological mechanism, methamphetamine self-administration, oral sucrose self-administration, chemogenetic neuromanipulation, and fiber photometry in mice were performed in this study.
Results
We reported that associative learning increased methamphetamine-induced self-administration, but not oral sucrose self-administration. In addition, the enhancement of methamphetamine-induced self-administration was independent of more methamphetamine consumption, and remained with higher drug-taking and motivation in the absence of visual cues, suggesting the direct effects of the associative learning that enhanced methamphetamine-induced self-administration. Moreover, chemogenetic inactivation of the secondary visual cortex (V2) reduced the enhancement of the drug-taking induced by associative learning but did not alter sucrose-taking. Further fiber photometry of V2 neurons demonstrated that methamphetamine-associative learning elicits V2 neuron excitation, and sucrose-associative learning elicits V2 neuron inhibition.
Conclusions
Therefore, this study reveals the neurobiological mechanism of V2 excitability underlying how associative learning participates in the formation of intractable memory related to drug addiction, and gives evidence to support V2 as a promising target for stimulation therapy for methamphetamine addiction.
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Data availability
Datasets from this study are available from the corresponding authors on reasonable request.
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Acknowledgements
This work was supported by National Key Research and Development Program of China (2023YFC3304201), Beijing Natural Science Foundation (7232106) and Young Elite Scientists Sponsorship Program by BAST (No. BYESS2023230).
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Dan-ni Cao, Ning Wu and Jin Li initiated this project and designed the study. Cai-ling Wang conducted the experiments and analyzed the data. Cai-ling Wang and Dan-ni Cao wrote and revised the manuscript. Ying-jie Zhu provided technical support.
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Wang, Cl., Cao, Dn., Wu, N. et al. The secondary visual cortex mediated the enhancement of associative learning on methamphetamine self-administration behaviors. Psychopharmacology (2024). https://doi.org/10.1007/s00213-024-06597-7
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DOI: https://doi.org/10.1007/s00213-024-06597-7