The Neurocircuitry of Substance Use Disorder, Treatment, and Change: A Resource for Clinical Psychiatrists.

Substance use disorder (SUD) is common in psychiatric patients and has a negative impact on health and well-being. However, SUD often goes untreated, and there is a need for psychiatrists, of all specialties, to address this pervasive clinical problem. In this review, the authors' goal is to provide a resource that describes treatments for SUD, using neuroscience as a framework.

Paternal morphine exposure enhances morphine self-administration and induces region-specific neural adaptations in reward-related brain regions of male offspring.

Background: A growing body of preclinical studies report that preconceptional experiences can have a profound and long-lasting impact on adult offspring behavior and physiology. However, less is known about paternal drug exposure and its effects on reward sensitivity in the next generation.

Methods: Adult male rats self-administered morphine for 65 days; controls received saline.

Exposure to environmental enrichment attenuates addiction-like behavior and alters molecular effects of heroin self-administration in rats.

Environmental factors profoundly affect the addictive potential of drugs of abuse and may also modulate the neuro-anatomical/neuro-chemical impacts of uncontrolled drug use and relapse propensity. This study examined the impact of environmental enrichment on heroin self-administration, addiction-related behaviors, and molecular processes proposed to underlie these behaviors. Male Sprague-Dawley rats in standard and enriched housing conditions intravenously self-administered similar amounts of heroin over 14 days.

Heroin-induced suppression of saccharin intake in OPRM1 A118G mice.

The single nucleotide polymorphism of the μ-opioid receptor, OPRM1 A118G, has been associated with greater drug and alcohol use, increased sensitivity to pain, and reduced sensitivity to the antinociceptive effects of opiates. In the present studies, we employed a 'humanized' mouse model containing the wild-type (118AA) or variant (118GG) allele to examine behavior in a model of heroin-induced devaluation of an otherwise palatable saccharin cue when repeated saccharin-heroin pairings occurred every 24h (Experiment 1) or every 48h (Experiment 2). The results showed that, while both the 118AA and 118GG mice demonstrated robust avoidance of the heroin-paired saccharin cue following daily taste-drug pairings, only the 118AA mice suppressed intake of the heroin-paired saccharin cue when 48h elapsed between each taste-drug pairing.

Once is too much: Early development of the opponent process in taste reactivity behavior is associated with later escalation of cocaine self-administration in rats.

Evidence suggests that the addiction process may begin immediately in some vulnerable subjects. Specifically, some rats have been shown to exhibit aversive taste reactivity (gapes) following the intraoral delivery of a cocaine-predictive taste cue after as few as 1-2 taste-drug pairings. After only 3-4 trials, the number of gapes becomes a reliable predictor of later cocaine self-administration.

Assessment of individual differences in the rat nucleus accumbens transcriptome following taste-heroin extended access.

Heroin addiction is a disease of chronic relapse that harms the individual through devaluation of personal responsibilities in favor of finding and using drugs. Only some recreational heroin users devolve into addiction but the basis of these individual differences is not known. We have shown in rats that avoidance of a heroin-paired taste cue reliably identifies individual animals with greater addiction-like behavior for heroin.

Reward devaluation and heroin escalation is associated with differential expression of CRF signaling genes.

One of the most damaging aspects of drug addiction is the degree to which natural rewards (family, friends, employment) are devalued in favor of seeking, obtaining and taking drugs. We have utilized an animal model of reward devaluation and heroin self-administration to explore the role of the coricotropin releasing factor (CRF) pathway. Given access to a saccharin cue followed by the opportunity to self-administer heroin, animals will parse into distinct phenotypes that suppress their saccharin intake (in favor of escalating heroin self-administration) or vice versa.

Greater avoidance of a heroin-paired taste cue is associated with greater escalation of heroin self-administration in rats.

Heroin addiction is a disease of chronic relapse affecting over half of its users. Therefore, modeling individual differences in addiction-like behavior is needed to better reflect the human condition. In a rodent model, avoidance of a cocaine-paired saccharin cue is associated with greater cocaine seeking and taking.

Cocaine-induced suppression of saccharin intake and morphine modulation of Ca²⁺ channel currents in sensory neurons of OPRM1 A118G mice.

Several studies have shown that human carriers of the single nucleotide polymorphism of the μ-opioid receptor, OPRM1 A118G, exhibit greater drug and alcohol use, increased sensitivity to pain, and reduced sensitivity to the antinociceptive effects of opiates. In the present study, we employed a 'humanized' mouse model containing the wild-type (118AA) or variant (118GG) allele to examine behavior in our model of drug-induced suppression of a natural reward cue and to compare the morphine pharmacological profile in acutely isolated sensory neurons. Compared with 118AA mice, our results demonstrate that homozygous 118GG mice exhibit greater avoidance of the cocaine-paired saccharin cue, a behavior linked to an aversive withdrawal-like state.

Once is too much: conditioned aversion develops immediately and predicts future cocaine self-administration behavior in rats.

Rats emit aversive taste reactivity (TR) behavior (i.e., gapes) following intraoral delivery of a cocaine-paired taste cue and greater conditioned aversive TR at the end of training predicts greater drug-seeking and taking.

Neuroglial expression of the MHCI pathway and PirB receptor is upregulated in the hippocampus with advanced aging.

The hippocampus undergoes changes with aging that impact neuronal function, such as synapse loss and altered neurotransmitter release. Nearly half of the aged population also develops deficits in spatial learning and memory. To identify age-related hippocampal changes that may contribute to cognitive decline, transcriptomic analysis of synaptosome preparations from adult (12 months) and aged (28 months) Fischer 344-Brown Norway rats assessed for spatial learning and memory was performed.