Unlocking the role of dorsal hippocampal α4β2 nicotinic acetylcholine receptors in Ethanol-Induced conditioned place preference in mice.

Neuroscience letters 2024 Feb 28

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Alcohol Use Disorder (AUD) presents a significant and challenging public health concern, marked by a dearth of effective pharmacological treatments. Understanding the neurobiological underpinnings of AUD is of paramount importance for the development of efficacious interventions. The process of addiction entails the acquisition of associative behaviors, prominently engaging the dorsal region of the hippocampus for encoding these associative memories. Nicotinic receptor systems have been implicated in mediating the rewarding effects of ethanol, as well as memory and learning processes. In our current investigation, we delved into the role of α4β2 nicotinic acetylcholine receptors (nAChRs) within the dorsal hippocampus in the context of ethanol-induced conditioned place preference (CPP), a robust model for scrutinizing the rewarding properties and drug-associated behaviors. To establish CPP, ethanol (2 g/kg) was administered intraperitoneally during a 8-day conditioning phase. Fos immunohistochemistry was employed to assess the involvement of discrete subregions within the dorsal hippocampus in ethanol-induced CPP. Additionally, we probed the influence of α4β2 nAChRs on CPP via microinjections of a selective nAChR antagonist, dihydro-β-erythroidine (DHBE, at dosages of 6, 12, and 18 µg/0.5 µL per hemisphere) within the hippocampus. Our results unveiled that ethanol-induced CPP was associated with an increase Fos -positive cells in various subregions of the dorsal hippocampus, including CA1, CA2, CA3, and the dentate gyrus. Intrahippocampal administration of DHBE (at doses of 6 and 18 µg/0.50 µL per hemisphere) effectively blocked ethanol-induced CPP, while leaving locomotor activity unaffected. These findings underscore the critical involvement of the dorsal hippocampus and α4β2 nAChRs in the acquisition of ethanol-associated learning and reward. Copyright © 2024 Elsevier B.V. All rights reserved.

Citation

Paola Palombo, Roberta Maeda, Caroline Riberti Zaniboni, Sheila Antonagi Engi, Thais Yokoyama, Natalia Bonetti Bertagna, Augusto Anesio, Paula Cristina Bianchi, Thamires Righi, Gabrielle Emily Boaventura Tavares, Caden Souccar, Fernando Bezerra Romualdo da Silva, Fabio Cardoso Cruz. Unlocking the role of dorsal hippocampal α4β2 nicotinic acetylcholine receptors in Ethanol-Induced conditioned place preference in mice. Neuroscience letters. 2024 Feb 28;824:137666