Dopamine Receptor Binding Predicts Clinical and Pharmacological Potencies of Antischizophrenic Drugs

Creese, Ian; Burt, David R.; Snyder, Solomon H.

doi:10.1126/science.3854

Cited by 2,094 publications

(827 citation statements)

References 17 publications

Supporting

Mentioning

780

Contrasting

Unclassified

Order By: Relevance

“…Indeed, the medications that have proven successful for treating schizophrenia/psychosis are drugs that primarily antagonize D 2 receptors [76,358]; however, most clinically effective antipsychotics also exhibit a myriad of other actions that contribute to both therapeutic and side-effect profiles [359,360]. …”

Section: Reviewmentioning

confidence: 99%

“…First-generation compounds, such as chlorpromazine and haloperidol, work primarily as D 2 receptor antagonists [358]. Second-generation, or ‘atypical,’ antipsychotics, such as clozapine (which has affinity for D 2 and D 4 receptors [426]), risperidone, olanzapine, and quetiapine, primarily affect DA and 5-HT systems, but with markedly reduced extrapyramidal side effects [427].…”

Section: Reviewmentioning

confidence: 99%

See 1 more Smart Citation

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

253

207

View full text Add to dashboard Cite

This review summarizes evidence of dysregulated reward circuitry function in a range of neurodevelopmental and psychiatric disorders and genetic syndromes. First, the contribution of identifying a core mechanistic process across disparate disorders to disease classification is discussed, followed by a review of the neurobiology of reward circuitry. We next consider preclinical animal models and clinical evidence of reward-pathway dysfunction in a range of disorders, including psychiatric disorders (i.e., substance-use disorders, affective disorders, eating disorders, and obsessive compulsive disorders), neurodevelopmental disorders (i.e., schizophrenia, attention-deficit/hyperactivity disorder, autism spectrum disorders, Tourette’s syndrome, conduct disorder/oppositional defiant disorder), and genetic syndromes (i.e., Fragile X syndrome, Prader–Willi syndrome, Williams syndrome, Angelman syndrome, and Rett syndrome). We also provide brief overviews of effective psychopharmacologic agents that have an effect on the dopamine system in these disorders. This review concludes with methodological considerations for future research designed to more clearly probe reward-circuitry dysfunction, with the ultimate goal of improved intervention strategies.

show abstract

Section: Reviewmentioning

confidence: 99%

Section: Reviewmentioning

confidence: 99%

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Dichter

Damiano

Allen

2012

J Neurodevelop Disord

253

207

View full text Add to dashboard Cite

show abstract

“…As DA has some excitatory actions at D1 receptors (Gerfen et al 1990;Gerfen 2000), D1 antagonists would tend to decrease the activity of target neurons in the nucleus accumbens, and as NMDA receptors are also excitatory, they would share this property with NMDA receptor antagonists. The psychotomimetic and psychostimulant actions of DA agonists, however, are known to be mediated through the D2 receptor subtype (Creese et al 1976;Ralph et al 1999;Caine et al 2000). As DA is inhibitory at D2 receptors (Gerfen et al 1990;Gerfen 2000), in this case it is D2 agonists that would share with NMDA antagonists the tendency to decrease activity in cells where D2 receptors and NMDA receptors are co-localized.…”

Section: Mechanisms Of Acpc Effects On the Acquisition Of Drug-conditmentioning

confidence: 99%

Selective Blockade of Drug-induced Place Preference Conditioning by ACPC, a Functional NDMA-receptor Antagonist

Papp

Gruca

Willner

2002

Neuropsychopharmacology

View full text Add to dashboard Cite

ACPC (1-aminocyclopropanecarboxylic acid) is a partial agonist at the strychnine-insensitive glycine receptor site on the NMDA receptor complex, and a functional NMDA antagonist. A series of experiments was conducted to assess the effects of ACPC in a biased place conditioning paradigm. As previously reported, ACPC itself did not support either appetitive or aversive place conditioning. However, co-administration of ACPC (200 mg/kg) blocked the acquisition of place preferences conditioned using a variety of psychoactive drugs (amphetamine, cocaine, nomifensine, diazepam, morphine, nicotine). No tolerance was seen to this effect following two weeks of chronic ACPC administration. Overall, ACPC did not affect the expression of place conditioning when administered immediately before the post-conditioning test. However, these effects appeared somewhat variable between drugs, and further analysis showed that ACPC did block the expression of preferences conditioned with some drugs (diazepam, morphine, nicotine), but not others (amphetamine, cocaine, nomifensine). The effects of ACPC could not be accounted for by state dependence, as ACPC blocked morphine and cocaine place preferences when administered during both the acquisition and the expression phase of conditioning. In contrast to the blockade by ACPC of drug-induced place preferences, ACPC had no effect on the acquisition of place preferences conditioned using a variety of natural non-drug reinforcers (food, sucrose, social interaction, novelty). ACPC also had no effect on the acquisition of drug-induced place aversions (naloxone, picrotoxin The treatment of drug addiction has two targets: cessation or reduction of use, and maintenance of those gains. During the maintenance phase, a number of factors have been identified that predispose to relapse. These include stimuli associated with drug taking (O'Brien et al. 1998). The place preference conditioning procedure has been used extensively as an animal model for investigating the rewarding properties of drug-conditioned stimuli. In this procedure, 27 , NO . 5 the animal experiences the effects of a drug while confined in a distinctive environment; subsequently the animal is offered a choice between the drug-paired environment and an environment that has been experienced in the drug-free state. Subject to certain methodological considerations, a preference for the drug-paired environment is interpreted to mean that the environment has acquired secondary reinforcing properties as a consequence of its pairing with a primary reinforcer. Drugs that support the development of a conditioned place preference (CPP) are generally those that are abused by people (e.g. psychostimulants, opioids, benzodiazepines, alcohol, nicotine), while drugs that do not support CPP are typically not abused (e.g. neuroleptics, antidepressants, antihistamines) (Carr et al. 1989;Schechter and Calcagnetti 1993;Calcagnetti and Schechter 1998;Tzschentke 1998). In addition to drug rewards, CPP can also be used to study the reinforcing prop...

show abstract

“…2 This hypothesis is partly based on the observation that the clinical efficacy of antipsychotic drugs correlates with their blocking affinities for the DA D 2 receptor. 3,4 In addition, psychostimulant drugs such as amphetamine (AMPH), which increase brain DA transmission, can induce and exacerbate psychotic symptoms in volunteers and schizophrenic patients, respectively. 5 Research on the etiology of schizophrenia has been focussed on possible dysfunctions within the major dopaminergic cell groups located in the ventral region of the midbrain (Mb) including the substantia nigra pars compacta (SNpc) (A9 cell group) and ventral tegmental area (VTA) (A10 cell group).…”

Section: Introductionmentioning

confidence: 99%

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

et al. 2007

View full text Add to dashboard Cite

The transcription factor Nurr1 (NR4A2) has been found to play a critical role in the development of midbrain dopaminergic neurons. Nurr1 heterozygous ( þ /À) male and female mice expressing 35-40% of normal levels of Nurr1 were generated and examined in animal models related to symptoms of schizophrenia. The Nurr1 ( þ /À) mice displayed hyperactivity in a novel environment, which persisted after administration of the dopamine-mimetic amphetamine and the N-methyl-D-aspartate receptor antagonist phencyclidine. The Nurr1 ( þ /À) mice were deficient in the retention of emotional memory and showed an enhanced response to swim stress. In addition, Nurr1 ( þ /À) male mice displayed a reduced dopamine turnover in the striatum and an enhanced dopamine turnover in the prefrontal cortex, while female mice showed an opposite pattern. These results show that Nurr1 ( þ /À) mice display a pattern of behaviors indicative of potential relevance for symptoms of schizophrenia combined with a gender-specific abnormal dopamine transmission in the striatum and prefrontal cortex, respectively. This suggests that the Nurr1 mutant mouse may be a potential animal model for studies on some of the behavioral and molecular mechanisms underlying schizophrenia.

show abstract

Dopamine Receptor Binding Predicts Clinical and Pharmacological Potencies of Antischizophrenic Drugs

Cited by 2,094 publications

References 17 publications

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Reward circuitry dysfunction in psychiatric and neurodevelopmental disorders and genetic syndromes: animal models and clinical findings

Selective Blockade of Drug-induced Place Preference Conditioning by ACPC, a Functional NDMA-receptor Antagonist

Adult mice with reduced Nurr1 expression: an animal model for schizophrenia

Contact Info

Product

Resources

About