Psychology Department, Michigan State University, Interdisciplinary Science and Technology Building, West Lab Rm 4100, 766 Service Rd, East Lansing, MI, 48824, USA.
Psychopharmacology (Berl). 2020 Sep;237(9):2823-2833. doi: 10.1007/s00213-020-05575-z. Epub 2020 Jun 29.
Drug use during adolescence results in a lifelong risk to develop substance-use disorders. Adolescent rats are less reactive to cocaine-associated cues compared with adults; however, the contribution of adolescent-formed, context-drug-associations to elicit relapse-like behavior is underexplored. Although it is known that social isolation can impact drug-seeking behavior, the effects of housing conditions on context-induced, cocaine-seeking during adolescence vs adulthood are unknown.
The present study compared the effect of adolescent vs adult-formed context-drug associations under different housing conditions (pair vs single) on cocaine-seeking behavior during adolescence or adulthood. This objective was accomplished using operant cocaine self-administration (Coc-SA) under a standard, non-abbreviated (Non-ABRV) or modified abbreviated (ABRV) paradigm.
In experiment 1, adolescent and adult rats received Non-ABRV Coc-SA in a distinct context (2 h, 1×/day, 10 days), and extinction training (EXT) in a second context (1 h, 1×/day, 8 days) with reinstatement test (TEST) during adulthood in the cocaine-paired context. In experiments 2 and 3, rats received all behavioral phases during adolescence or adulthood: ABRV Coc-SA (2 h, 2×/day, 5 days), EXT (1 h, 4×/day, 2 days) with TEST in a cocaine-paired or novel, unpaired context. All experiments included pair and single-housing conditions.
Age at cocaine exposure did not influence behavior in Non-ABRV or ABRV paradigms. Under Non-ABRV conditions, adolescent and adult single-housed rats had higher seeking behavior than pair housed. These data suggest that social isolation influences context-induced, cocaine-seeking regardless of age at drug exposure and provides a condensed, ABRV paradigm to investigate context-induced, cocaine-seeking behavior during adolescence.
青少年时期的药物使用会导致终生罹患物质使用障碍的风险。与成年大鼠相比,青春期大鼠对可卡因相关线索的反应性较低;然而,青春期形成的、与环境相关的药物关联引发类似复发的行为的贡献仍未得到充分探索。虽然已知社交隔离会影响觅药行为,但住房条件对青春期和成年期环境诱发可卡因觅药的影响尚不清楚。
本研究比较了不同住房条件(成对或单独)下青少年和成年形成的环境药物关联对青春期或成年期可卡因觅药行为的影响。这一目标是通过标准的非缩写(Non-ABRV)或改良缩写(ABRV)范式下的操作性可卡因自我给药(Coc-SA)来实现的。
在实验 1 中,青少年和成年大鼠在特定环境中接受 Non-ABRV Coc-SA(2 小时,1×/天,10 天),并在第二个环境中接受 EXT(1 小时,1×/天,8 天),然后在成年期在可卡因配对环境中进行 TEST。在实验 2 和 3 中,大鼠在青春期或成年期接受所有行为阶段:ABRV Coc-SA(2 小时,2×/天,5 天),EXT(1 小时,4×/天,2 天),然后在可卡因配对或新的、未配对的环境中进行 TEST。所有实验均包括成对和单独饲养条件。
可卡因暴露的年龄并不影响 Non-ABRV 或 ABRV 范式中的行为。在 Non-ABRV 条件下,青少年和成年独居大鼠的觅药行为高于群居大鼠。这些数据表明,社交隔离会影响环境诱发的可卡因觅药,而与药物暴露时的年龄无关,并提供了一个浓缩的 ABRV 范式,以研究青春期环境诱发的可卡因觅药行为。