Current perspectives on selective dopamine D3 receptor antagonists as pharmacotherapeutics for addictions and related disorders DOI
Christian Heidbreder, Amy Hauck Newman

Annals of the New York Academy of Sciences, Journal Year: 2010, Volume and Issue: 1187(1), P. 4 - 34

Published: Jan. 8, 2010

Repeated exposure to drugs of abuse produces long‐term molecular and neurochemical changes that may explain the core features addiction, such as compulsive seeking taking drug, well risk relapse. A growing number new cellular targets addictive have been identified, rapid advances are being made in relating those specific behavioral phenotypes animal models addiction. In this context, pattern expression dopamine (DA) D 3 receptor rodent human brain response contributed primarily direct research efforts toward development selective DA antagonists. Growing preclinical evidence indicates these compounds actually regulate motivation self‐administer disrupt drug‐associated cue‐induced craving. This report will be divided into three parts. First, support efficacy antagonists drug addiction reviewed. The effects mixed 2 /D not discussed here because most low selectivity at versus receptor, their profile is related functional antagonism receptors possibly interactions with other neurotransmitter systems. Second, major medicinal chemistry for identification optimization partial agonists analyzed. Third, translational from studies so‐called proof‐of‐concept indications discussed.

Language: Английский

REVIEW ON CPP: Measuring reward with the conditioned place preference (CPP) paradigm: update of the last decade DOI
Thomas Tzschentke

Addiction Biology, Journal Year: 2007, Volume and Issue: 12(3-4), P. 227 - 462

Published: July 30, 2007

ABSTRACT Conditioned place preference (CPP) continues to be one of the most popular models study motivational effects drugs and non‐drug treatments in experimental animals. This is obvious from a steady year‐to‐year increase number publications reporting use this model. Since compilation preceding review 1998, more than 1000 new studies using conditioning have been published, aim present provide an overview these recent publications. There are trends developments that literature last decade. First, as knockout transgenic animals become available, increasingly used assess or rewards genetically modified Second, there still small but growing on aspects pain, field pre‐clinical research has so far received little attention, because lack appropriate animal models. Third, widely tolerance sensitization rewarding induced by pre‐treatment regimens. Fourth, extinction/reinstatement procedures becoming popular. interesting approach thought model certain relapse addictive behavior previously almost exclusively studied drug self‐administration paradigms. It now also established provides additional technically easy important phenomenon. The enormous covered prevented in‐depth discussion many methodological, pharmacological neurobiological aspects; large extent, presentation data had limited short condensed summary relevant findings.

Language: Английский

Citations

1295
The glutamate homeostasis hypothesis of addiction DOI
Peter W. Kalivas

Nature reviews. Neuroscience, Journal Year: 2009, Volume and Issue: 10(8), P. 561 - 572

Published: July 1, 2009

Language: Английский

Citations

1281
Reward Processing by the Opioid System in the Brain DOI
Julie Le Merrer, Jérôme A. J. Becker, Katia Befort

et al.

Physiological Reviews, Journal Year: 2009, Volume and Issue: 89(4), P. 1379 - 1412

Published: Sept. 29, 2009

The opioid system consists of three receptors, mu, delta, and kappa, which are activated by endogenous peptides processed from protein precursors, proopiomelanocortin, proenkephalin, prodynorphin. Opioid receptors recruited in response to natural rewarding stimuli drugs abuse, both opioids their modified as addiction develops. Mechanisms whereby aberrant activation modifications the contribute drug craving relapse remain be clarified. This review summarizes our present knowledge on brain sites where controls hedonic responses is abuse rodent brain. We 1) latest data anatomy system, 2) consequences local intracerebral pharmacological manipulation reinforced behaviors, 3) gene knockout behaviors dependence, 4) chronic exposure expression levels genes. Future studies will establish key molecular actors neural onset addictive disorders. Combined with human nonhuman primate (not reviewed here), research this extremely active field has implications for understanding biology therapeutic interventions treat disorder.

Language: Английский

Citations

941
Long-term depression in the CNS DOI
Graham L. Collingridge, Stéphane Peineau, John G. Howland

et al.

Nature reviews. Neuroscience, Journal Year: 2010, Volume and Issue: 11(7), P. 459 - 473

Published: June 18, 2010

Language: Английский

Citations

860
The role of impulsive behavior in drug abuse DOI

Jennifer L. Perry,

Marilyn E. Carroll

Psychopharmacology, Journal Year: 2008, Volume and Issue: 200(1), P. 1 - 26

Published: July 4, 2008

Language: Английский

Citations

783
Drug Addiction as a Pathology of Staged Neuroplasticity DOI Open Access
Peter W. Kalivas,

Charles P. O’Brien

Neuropsychopharmacology, Journal Year: 2007, Volume and Issue: 33(1), P. 166 - 180

Published: Sept. 5, 2007

Language: Английский

Citations

726
Extinction circuits for fear and addiction overlap in prefrontal cortex DOI Open Access
Jamie Peters, Peter W. Kalivas, Gregory J. Quirk

et al.

Learning & Memory, Journal Year: 2009, Volume and Issue: 16(5), P. 279 - 288

Published: April 20, 2009

Extinction is a form of inhibitory learning that suppresses previously conditioned response. Both fear and drug seeking are responses can lead to maladaptive behavior when expressed inappropriately, manifesting as anxiety disorders addiction, respectively. Recent evidence indicates the medial prefrontal cortex (mPFC) critical for extinction both drug-seeking behaviors. Moreover, dorsal-ventral distinction apparent within mPFC, such prelimbic (PL-mPFC) drives expression seeking, whereas infralimbic (IL-mPFC) these behaviors after extinction. For fear, dichotomy accomplished via divergent projections different subregions amygdala, it nucleus accumbens. Given mPFC represents common node in circuit behaviors, treatments target this region may help alleviate symptoms addictive by enhancing memory.

Language: Английский

Citations

710
Drug Wanting: Behavioral Sensitization and Relapse to Drug-Seeking Behavior DOI

Jeffery D. Steketee,

Peter W. Kalivas

Pharmacological Reviews, Journal Year: 2011, Volume and Issue: 63(2), P. 348 - 365

Published: April 13, 2011

Repeated exposure to drugs of abuse enhances the motor-stimulant response these drugs, a phenomenon termed behavioral sensitization. Animals that are extinguished from self-administration training readily relapse drug, conditioned cue, or stress priming. The involvement sensitization in reinstated drug-seeking behavior remains controversial. This review describes and drug seeking as events, neural circuitry, neurochemistry, neuropharmacology underlying both models will be described, compared, contrasted. It seems although reinstatement involve overlapping circuitry neurotransmitter receptor systems, role ill-defined. Nevertheless, it is argued useful model for determining basis addiction, an example provided which data studies led potential pharmacotherapies have been tested animal human addicts.

Language: Английский

Citations

637
Neurobiology of the incubation of drug craving DOI
Charles L. Pickens, Mikko Airavaara,

Florence Theberge

et al.

Trends in Neurosciences, Journal Year: 2011, Volume and Issue: 34(8), P. 411 - 420

Published: July 24, 2011

Language: Английский

Citations

624
The Nucleus Accumbens: Mechanisms of Addiction across Drug Classes Reflect the Importance of Glutamate Homeostasis DOI Open Access
Michael D. Scofield, Jasper A. Heinsbroek, Cassandra D. Gipson

et al.

Pharmacological Reviews, Journal Year: 2016, Volume and Issue: 68(3), P. 816 - 871

Published: June 30, 2016

The nucleus accumbens is a major input structure of the basal ganglia and integrates information from cortical limbic structures to mediate goal-directed behaviors. Chronic exposure several classes drugs abuse disrupts plasticity in this region, allowing drug-associated cues engender pathologic motivation for drug seeking. A number alterations glutamatergic transmission occur within after withdrawal chronic exposure. These drug-induced neuroadaptations serve as molecular basis relapse vulnerability. In review, we focus on role that glutamate signal transduction plays addiction-related First, explore accumbens, including cell types neuronal populations present well afferent efferent connections. Next discuss rodent models addiction assess viability these testing candidate pharmacotherapies prevention relapse. Then provide review literature describing how synaptic altered also pharmacological manipulation systems can inhibit seeking laboratory setting. Finally, examine results clinical trials which designed manipulate have been effective treating human patients. Further elucidation alter will be necessary development new therapeutics treatment across all addictive substances.

Language: Английский

Citations

528