Kristian Adamatzky, Angharad C Collins, Aldo Badiani, Bryan F Singer
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引用次数: 0
Abstract
Rationale: Animal models of addiction often study changes in motivation after repeated self-administration of a single drug. However, human users frequently consume multiple drugs, potentially altering their motivation and affective response.
Objectives: This study investigated how individual rats differentially self-administer cocaine and heroin, and whether motivation to take each drug was associated with affective states, as indicated by ultrasonic vocalisations (USVs). We also determined whether opioid antagonism (via naltrexone), which is known to decrease heroin-taking and associated USVs, also altered motivation and vocalisations for cocaine.
Methods: Male Lister Hooded rats, with surgically implanted catheters, self-administered cocaine and heroin on alternating days. Motivation was evaluated via drug intake escalation (fixed-ratio schedule), behavioural adaptation to dose reductions (behavioural economics), and progressive ratio breakpoints (with or without naltrexone). USVs were recorded and analysed using machine learning software (DeepSqueak).
Results: Rats escalated intake of both drugs during training. At the start of each session, rats rapidly self-administered cocaine or heroin; this drug-loading behaviour was associated with an increase in 50 kHz vocalisations. Rats altered their cocaine and heroin intake when drug doses decreased, and this was accompanied by reduced 50 kHz USVs. Lastly, naltrexone reduced progressive ratio breakpoints for heroin but not cocaine; naltrexone also decreased 50 kHz USVs for heroin (an effect which persisted).
Conclusions: Distinct patterns emerged in motivation and USVs between cocaine and heroin self-administration. Notably, USV frequency did not consistently align with motivation, especially when drug dosage changed. Future research may clarify this divergence.
期刊介绍：
Official Journal of the European Behavioural Pharmacology Society (EBPS)
Psychopharmacology is an international journal that covers the broad topic of elucidating mechanisms by which drugs affect behavior. The scope of the journal encompasses the following fields:
Human Psychopharmacology: Experimental
This section includes manuscripts describing the effects of drugs on mood, behavior, cognition and physiology in humans. The journal encourages submissions that involve brain imaging, genetics, neuroendocrinology, and developmental topics. Usually manuscripts in this section describe studies conducted under controlled conditions, but occasionally descriptive or observational studies are also considered.
Human Psychopharmacology: Clinical and Translational
This section comprises studies addressing the broad intersection of drugs and psychiatric illness. This includes not only clinical trials and studies of drug usage and metabolism, drug surveillance, and pharmacoepidemiology, but also work utilizing the entire range of clinically relevant methodologies, including neuroimaging, pharmacogenetics, cognitive science, biomarkers, and others. Work directed toward the translation of preclinical to clinical knowledge is especially encouraged. The key feature of submissions to this section is that they involve a focus on clinical aspects.
Preclinical psychopharmacology: Behavioral and Neural
This section considers reports on the effects of compounds with defined chemical structures on any aspect of behavior, in particular when correlated with neurochemical effects, in species other than humans. Manuscripts containing neuroscientific techniques in combination with behavior are welcome. We encourage reports of studies that provide insight into the mechanisms of drug action, at the behavioral and molecular levels.
Preclinical Psychopharmacology: Translational
This section considers manuscripts that enhance the confidence in a central mechanism that could be of therapeutic value for psychiatric or neurological patients, using disease-relevant preclinical models and tests, or that report on preclinical manipulations and challenges that have the potential to be translated to the clinic. Studies aiming at the refinement of preclinical models based upon clinical findings (back-translation) will also be considered. The journal particularly encourages submissions that integrate measures of target tissue exposure, activity on the molecular target and/or modulation of the targeted biochemical pathways.
Preclinical Psychopharmacology: Molecular, Genetic and Epigenetic
This section focuses on the molecular and cellular actions of neuropharmacological agents / drugs, and the identification / validation of drug targets affecting the CNS in health and disease. We particularly encourage studies that provide insight into the mechanisms of drug action at the molecular level. Manuscripts containing evidence for genetic or epigenetic effects on neurochemistry or behavior are welcome.
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