In abstinent drug addicts, cues formerly associated with drug-taking experiences gain relapse-inducing potency ('') over time. Animal models of incubation may help develop treatments to prevent relapse, but these models have ubiquitously focused on the role of conditioned stimuli (CSs) signaling drug delivery. Discriminative stimuli (DSs) are unique in that they exert stimulus-control over both drug taking and drug seeking behavior and are difficult to extinguish. For this reason, incubation of the excitatory effects of DSs that signal drug availability, not yet examined in preclinical studies, could be relevant to relapse prevention. We trained rats to self-administer cocaine (or palatable food) under DS control, then investigated DS-controlled incubation of craving, in the absence of drug-paired CSs. DS-controlled cocaine (but not palatable food) seeking incubated over 60 days of abstinence and persisted up to 300 days. Understanding the neural mechanisms of this DS-controlled incubation holds promise for drug relapse treatments.
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http://dx.doi.org/10.7554/eLife.44427 | DOI Listing |
Organisms continually tune their perceptual systems to the features they encounter in their environment . We have studied how ongoing experience reorganizes the synaptic connectivity of neurons in the olfactory (piriform) cortex of the mouse. We developed an approach to measure synaptic connectivity , training a deep convolutional network to reliably identify monosynaptic connections from the spike-time cross-correlograms of 4.
View Article and Find Full Text PDFJ Affect Disord
January 2025
Department of Psychiatry, University of Oxford, Warneford Ln, Headington, Oxford OX3 7JX, United Kingdom; Oxford Health NHS Foundation Trust, Warneford Ln, Headington, Oxford OX3 7JX, United Kingdom. Electronic address:
Background: The renin angiotensin system (RAS) is implicated in various cognitive processes relevant to anxiety. However, the role of the RAS in pattern separation, a hippocampal memory mechanism that enables discrete encoding of similar stimuli, is unclear. Given the proposed role of this mechanism in overgeneralization and the maintenance of anxiety, we explored the influence of the RAS on mnemonic discrimination i.
View Article and Find Full Text PDFDiagnostics (Basel)
January 2025
Institute of Higher Nervous Activity and Neurophysiology, Russian Academy of Sciences, 117465 Moscow, Russia.
The link between serotonergic modulation and depression is under debate; however, serotonin reuptake inhibitors (SRIs) are still the first-choice medicine in this condition. Disturbances in time perception are also reported in depression with one of the behavioral schedules used to study interval timing, differential-reinforcement-learning-of-low-rate, having been shown to have high predictive validity for an antidepressant effect. Here, we introduce an IntelliCage research protocol of an interval bisection task that allows more ecologically valid and less time-consuming rodent examination and provides an example of its use to confirm the previously reported acute effect of an SRI, clomipramine, on interval timing (increase in bisection point, D50).
View Article and Find Full Text PDFBr J Anaesth
January 2025
Department of Anaesthesiology, Peking University First Hospital, Beijing, China; Outcomes Research Consortium, Cleveland, OH, USA.
Background: The Qnox index is a novel monitor to quantify intraoperative nociception based on an electroencephalographic algorithm. We evaluated the ability of the Qnox index to discriminate noxious from non-noxious stimuli, respond to stimuli, and discriminate different levels of analgesia in patients under propofol anaesthesia with neuromuscular block.
Methods: Qnox was compared with heart rate and mean arterial pressure with five designated stimuli: tetanic stimulations without (tetanic 1) and with sufentanil (tetanic 2), skin incision, tracheal intubation, and a non-noxious period.
Curr Biol
January 2025
Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA; Medical Discovery Team on Addiction, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address:
Adaptive behavior in a dynamic environmental context often requires rapid revaluation of stimuli that deviates from well-learned associations. The divergence between stable value-encoding and appropriate behavioral output remains a critical component of theories of dopamine's function in learning, motivation, and motor control. Yet, how dopamine neurons are involved in the revaluation of cues when the world changes, to alter our behavior, remains unclear.
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