PMID- 32717403 OWN - NLM STAT- MEDLINE DCOM- 20210427 LR - 20211002 IS - 1090-2139 (Electronic) IS - 0889-1591 (Print) IS - 0889-1591 (Linking) VI - 89 DP - 2020 Oct TI - Expression of a heroin contextually conditioned immune effect in male rats requires CaMKIIalpha-expressing neurons in dorsal, but not ventral, subiculum and hippocampal CA1. PG - 414-422 LID - S0889-1591(20)30917-X [pii] LID - 10.1016/j.bbi.2020.07.028 [doi] AB - The physiological and motivational effects of heroin and other abused drugs become associated with environmental (contextual) stimuli during repeated drug use. As a result, these contextual stimuli gain the ability to elicit drug-like conditioned effects. For example, after context-heroin pairings, exposure to the heroin-paired context alone produces similar effects on peripheral immune function as heroin itself. Conditioned immune effects can significantly exacerbate the adverse health consequences of heroin use. Our laboratory has shown that exposure to a heroin-paired context suppresses lipopolysaccharide (LPS)-induced splenic nitric oxide (NO) production in male rats, and this effect is mediated in part by the dorsal hippocampus (dHpc). However, specific dHpc output regions, whose efferents might mediate conditioned immune effects, have not been identified, nor has the contribution of ventral hippocampus (vHpc) been investigated. Here, we evaluated the role of CaMKIIalpha-expressing neurons in the dHpc and vHpc main output regions by expressing G(i)-coupled designer receptors exclusively activated by designer drugs (DREADDs) under a CaMKIIalpha promoter in the dorsal subiculum and CA1 (dSub, dCA1) or ventral subiculum and CA1 (vSub, vCA1). After context-heroin conditioning, clozapine-N-oxide (CNO, DREADD agonist) or vehicle was administered systemically prior to heroin-paired context (or home-cage control) exposure and LPS immune challenge. Chemogenetic inhibition of CaMKIIalpha-expressing neurons in dHpc, but not vHpc, output regions attenuated the expression of conditioned splenic NO suppression. These results establish that the main dHpc output regions, the dSub and dCA1, are critical for this context-heroin conditioned immune effect. CI - Published by Elsevier Inc. FAU - Lebonville, Christina L AU - Lebonville CL AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, CB#3270, Chapel Hill, NC 27599-3270 USA. FAU - Paniccia, Jacqueline E AU - Paniccia JE AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, CB#3270, Chapel Hill, NC 27599-3270 USA. FAU - Parekh, Shveta V AU - Parekh SV AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, CB#3270, Chapel Hill, NC 27599-3270 USA. FAU - Wangler, Lynde M AU - Wangler LM AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, CB#3270, Chapel Hill, NC 27599-3270 USA. FAU - Jones, Meghan E AU - Jones ME AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, CB#3270, Chapel Hill, NC 27599-3270 USA. FAU - Fuchs, Rita A AU - Fuchs RA AD - Integrative Physiology and Neuroscience, College of Veterinary Medicine, Washington State University, P.O. Box 647620, Pullman, WA 99164-7620, USA. FAU - Lysle, Donald T AU - Lysle DT AD - Department of Psychology and Neuroscience, University of North Carolina at Chapel Hill, CB#3270, Chapel Hill, NC 27599-3270 USA. Electronic address: dlysle@email.unc.edu. LA - eng GR - F31 DA047054/DA/NIDA NIH HHS/United States GR - R01 DA025646/DA/NIDA NIH HHS/United States GR - R01 DA034721/DA/NIDA NIH HHS/United States GR - T32 DA007244/DA/NIDA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20200724 PL - Netherlands TA - Brain Behav Immun JT - Brain, behavior, and immunity JID - 8800478 RN - 70D95007SX (Heroin) SB - IM MH - Animals MH - Conditioning, Classical MH - *Heroin MH - *Hippocampus MH - Male MH - Neurons MH - Rats PMC - PMC7572614 MID - NIHMS1618266 OTO - NOTNLM OT - Chemogenetics OT - DREADD OT - Heroin OT - Hippocampus OT - Immune conditioning OT - Learning OT - Nitric oxide OT - Opioid EDAT- 2020/07/28 06:00 MHDA- 2021/04/28 06:00 PMCR- 2021/10/01 CRDT- 2020/07/28 06:00 PHST- 2020/05/11 00:00 [received] PHST- 2020/07/16 00:00 [revised] PHST- 2020/07/20 00:00 [accepted] PHST- 2020/07/28 06:00 [pubmed] PHST- 2021/04/28 06:00 [medline] PHST- 2020/07/28 06:00 [entrez] PHST- 2021/10/01 00:00 [pmc-release] AID - S0889-1591(20)30917-X [pii] AID - 10.1016/j.bbi.2020.07.028 [doi] PST - ppublish SO - Brain Behav Immun. 2020 Oct;89:414-422. doi: 10.1016/j.bbi.2020.07.028. Epub 2020 Jul 24.