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CNS Receptors for Opioids
Published in Edythe D. London, Imaging Drug Action in the Brain, 2017
Richard J. Knopp, Mary Hunt, James K. Wamsley, Henry I. Yamamura
The addiction liability of opiates has been correlated with their positive reinforcement activity in a variety of behavioral tests. This is demonstrated by the tendency of animals implanted with intraventricular injection cannuli to self-administer opioids into the brain (Amit et al., 1976; Belluzzi and Stein, 1977). Initial studies (Bozarth and Wise, 1981) showed that rats quickly learn to self-administer morphine into the ventral tegmental area identifying this as an important location for opioid-induced behavioral reward. Opioid action at this site appears to be essential for this reward effect since self-administration of i.v. heroin is antagonized by injections of the hydrophilic opioid antagonist, diallyl-normorphinium bromide at the ventral tegmentum, but not at the nucleus accumbens septi or central striatum (Britt and Wise, 1983). The results of this study suggest that opioid action at the ventral tegmental area is required for the positive reinforcing effect of opiates, but there is also evidence for the involvement of other brain areas (see below). The region of the ventral tegmentum involved in the mediation of opioid reward was localized from the stereotaxic placement of cannuli supporting morphine-induced conditioned place preference (Bozarth, 1987). These studies showed that the ventral tegmental sites at which morphine induces conditioned place preference correspond closely with that of the A10 nucleus containing dopamine neurons (Bozarth, 1987).
What Neurobiology Has to Say About Why People Abuse Alcohol and Other Drugs
Published in Richard T. Spence, Diana M. DiNitto, Shulamith Lala Ashenberg Straussner, Neurobiology of Addictions, 2014
In 1987, Wise and Bozarth observed that all the drugs that lead to compulsive use share a capacity for inducing dopamine release in the ventral tegmental area of the brain which projects to the prefrontal cortex, the nucleus accumbens, the ventral palladium, and other structures. Moreover, all of these compulsive use-inducing substances satisfy the definition of a reinforcer, since animals will work for their administration and these drugs can be used to induce conditioned place preference, i.e., animals will prefer to spend time in locations where they previously received these drugs. Although behaviorists had long cautioned against the inference that reinforcers are necessarily associated with enjoyment, it was easy to leap to the conclusion that a substance for which animals will work, or which induce conditioned place preference, are enjoyed. Additionally, some concluded that since drugs that lead to compulsive use also increase dopamine activity, and because dopaminergic tracts overlap with brain areas for electrical self-stimulation, dopamine is the brain’s pleasure neurotransmitter, i.e., dopamine is the brain’s pleasure neurotransmitter (Wise & Rompre, 1989).
ENTRIES A–Z
Published in Philip Winn, Dictionary of Biological Psychology, 2003
A form of ASSOCIATIVE LEARNING that requires an animal to approach a location that has been previously associated with a REWARD or avoid a location hat has been associated with PUNISHMENT. The general conditioned place preference paradigm consists of an apparatus with two compartments, each compartment exhibiting distinct visuo-spatial and tactile cues (for instance, black vs. white compartment; smooth vs. rough floor). During the initial phase of positive place preference conditioning, the animal is confined to one of the compartments either where a reward is administered (which will be the paired compartment) or the compartment where no reward is administered (the unpaired compartment) on separate days. This procedure is normally repeated over four to ten days (though in some cases, for even longer). The compartments that are paired and unpaired with reward remain consistent over the course of training. On the test day, no reward is presented. The animal is placed in a neutral compartment that is connected to both the paired and unpaired sides of the apparatus, and is allowed to move freely through both compartments. The presence of a conditioned place preference is observed when the animals spend a greater amount of time in the compartment that was previously paired with the reward, relative to the compartment where no reward was administered. Thus, the compartment where reward was received previously becomes a conditioned reinforcer (see CONDITIONED REINFORCEMENT) to the animal. Place conditioning can be established using a variety of natural and artificial rewarding stimuli, such as food, water, sexually receptive mates, PSYCHOMOTOR STIMULANTS and OPIATES. This paradigm is useful in assessing the rewarding effects of drugs of abuse. LESIONS or pharmacological manipulations are said to effect the ACQUISITION of place conditioning if administration of such treatments during the conditioning phase has an effect on the magnitude of place preference exhibited on the test day. Alternatively, treatments effect the expression of place conditioning if they effect the magnitude of place preference exhibited on the test day when administered after the conditioning phase.
Kratom as an opioid alternative: harm, or harm reduction? A systematic review of literature
Published in The American Journal of Drug and Alcohol Abuse, 2022
Cornel Stanciu, Saeed Ahmed, Samantha Gnanasegaram, Stephen Gibson, Thomas Penders, Oliver Grundmann, Christopher McCurdy
Two studies in addition to those by Wilson et al. mentioned in the above section assessed reinforcing properties through induction of conditioned place preference. The first also assessed drug substitution and found that morphine and MG fully substituted for methamphetamine (44). MG however was found to only induce CPP at higher doses, and when coadministered with morphine. MG also attenuated acquisition and expression of morphine induced CPP in a dose-dependent fashion. The second study assessed the impact of MG on extinguished opioid induced CPP in rats, as well as cross-reinstatement with morphine (45). When MG and morphine were injected in rats that previously extinguished a morphine or MG induced CPP, respectively, a dose-dependent reinstatement was noted. The authors conclude that MG and morphine have a similar mechanism in reward/motivating properties and a priming exposure to mitragynine in an opioid remitted organism may cause relapse to the previously abused drug.
The effect of prescribing antibiotics with opioids on the development of opioid use disorder: a national database study
Published in Journal of Addictive Diseases, 2022
Zachary G. Freedman, Jennifer A. Kane, Tonya S. King, Nicholas M. Graziane
In addition to opioids, there is evidence that antibiotics modify the gut microbiome, eliciting either a negative (pathogenic) or positive impact (i.e., eubiotic effect).9 This modification is dependent upon the class (bacterial targets), pharmacokinetic profile, pharmacodynamics, dose, duration, and route of administration.9 Preclinical studies of substance use disorders, employing the conditioned place preference paradigm, a model of drug reward and drug-context associations, have shown that antibiotic treatment blocks cocaine (10 mg/kg)-induced conditioned place preference.10,11 Additionally, preclinical research has shown that the β-lactam antibiotic, ceftriaxone, is effective at attenuating drug-seeking behaviors.12,13 Based on the observed protective effects of antibiotics on addiction like behaviors in preclinical models of substance use disorders, we sought to investigate whether antibiotic co-treatment with opioids in a hospital or emergency department setting influenced the risk of developing OUD 12 months following discharge from the hospital. For this investigation, we employed TriNetX electronic medical records. TriNetX is a third-party software product that provides access to a clinical data network consisting of 170 healthcare organizations across 30 countries.14 Here, we employed TriNetX to test the hypothesis that antibiotics prescribed with opioids in the hospital setting were associated with a protective effect against developing OUD following discharge from the hospital.
Systematic review of preclinical, clinical, and post-marketing evidence of bupropion misuse potential
Published in The American Journal of Drug and Alcohol Abuse, 2019
Andrew C Naglich, E. Sherwood Brown, Bryon Adinoff
Conditioned place preference (CPP) studies determine if animal subjects given an investigational drug demonstrate any preference for the environment associated with the drug over other environments. Laboratory animals are dosed with a given drug, and are placed in one of two distinctly designed outer compartments of a three-compartment chamber for several training periods. These periods are alternated with administration of the injection vehicle and placement in the alternate experimental chamber. Following training, the animals are placed in the central chamber and given access to the two training chambers and then assessed for amount of time spent in the respective experimental chambers. CPP is present if the animal spends significantly more time in one experimental chamber compared to the other.