Role of perineuronal nets in the anterior dorsal lateral hypothalamic area in the acquisition of cocaine-induced conditioned place preference and self-administration.
Addiction involves drug-induced neuroplasticity in the circuitry of motivated behavior, which includes the medial forebrain bundle and the lateral hypothalamic area. Emerging at the forefront of neuroplasticity regulation are specialized extracellular matrix (ECM) structures that form perineuronal nets (PNNs) around certain neurons, mainly parvalbumin positive (PV+), fast-spiking interneurons (FSINs), making them a promising target for the regulation of drug-induced neuroplasticity. Despite the emerging significance of PNNs in drug-induced neuroplasticity and the well-established role of the lateral hypothalamic area (LHA) in reward, reinforcement, and motivation, very little is known about how PNN-expressing neurons control drug-seeking behavior. We found that a discrete region of the anterior dorsal LHA (LHAad) exhibited robust PNN and dense ECM expression. Approximately 87% of parvalbumin positive (PV+) neurons co-expressed the PNN marker Wisteria floribunda agglutinin (WFA), while 62% of WFA positive (WFA+) neurons co-expressed PV in the LHAad of drug naïve rats. Removal of PNNs within this brain region via chrondroitinase ABC (Ch-ABC) administration abolished acquisition of cocaine-induced CPP and significantly attenuated the acquisition of cocaine self-administration (SA). Removal of LHAad PNNs did not affect locomotor activity, sucrose intake, sucrose-induced CPP, or acquisition of sucrose SA in separate groups of cocaine naïve animals. These data suggest that PNN-dependent neuroplasticity within the LHAad is critical for the acquisition of both cocaine-induced CPP and SA but is not general to all rewards, and that PNN degradation may have utility for the management of drug-associated behavioral plasticity and memory in cocaine addicts.
Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, United States. Electronic address: jordan.blacktop@wsu.edu.
Jordan M
JM
Blacktop
Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, United States.
Ryan P
RP
Todd
Department of Integrative Physiology and Neuroscience, Washington State University, Vancouver, WA, United States.
Barbara A
BA
Sorg
D000779:Anesthetics, Local / Q000494:pharmacology*; D000818:Animals; D019765:Chondroitin ABC Lyase / Q000378:metabolism; D011508:Chondroitin Sulfate Proteoglycans / Q000378:metabolism; D003042:Cocaine / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects*; D003463:Cues; D005108:Extinction, Psychological / Q000187:drug effects; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects; D007026:Hypothalamic Area, Lateral / Q000166:cytology* / Q000187:drug effects; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010320:Parvalbumins / Q000378:metabolism; D037121:Plant Lectins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D034781:Receptors, N-Acetylglucosamine / Q000378:metabolism; D012054:Reinforcement, Psychology; D012646:Self Administration; D013997:Time Factors
D000779:Anesthetics, Local; D011508:Chondroitin Sulfate Proteoglycans; D010320:Parvalbumins; D037121:Plant Lectins; D034781:Receptors, N-Acetylglucosamine; C040129:wisteria lectin; D019765:Chondroitin ABC Lyase; D003042:Cocaine
Addiction; Cocaine; Conditioned place preference; Dorsal anterior lateral hypothalamic area; Drug-associated memory; Extracellular matrix; Perineuronal nets; Self-administration