Abstract:
RATIONALE:There is an emerging body of evidence that implicates a crucial role of γ-aminobutyric acid subtype A (GABAA) receptors in modulating the rewarding effects of a number of abused drugs. Modulation of GABAA receptors may therefore represent a novel drug-class independent mechanism for the development of abuse treatment pharmacotherapeutics. OBJECTIVES:We tested the hypothesis that the GABAA receptor benzodiazepine-site (BDZ) negative modulator Ro15-4513 would reduce the reward-related effects of three pharmacologically dissimilar drugs; toluene vapor, d-methamphetamine, and diazepam using intracranial self-stimulation (ICSS) in mice. We also examined whether Ro15-4513 attenuated dopamine release produced by d-methamphetamine in an in vivo microdialysis procedure. RESULTS:Ro15-4513 abolished ICSS reward facilitation produced by all three abused drugs at Ro15-4513 doses which had no effect on ICSS when administered alone. In contrast, the BDZ antagonist flumazenil only attenuated the ICSS-facilitating effects of diazepam. Administration of the same dose of Ro15-4513 which abolished drug-facilitated ICSS produced a 58 % decrease in d-methamphetamine-stimulated dopamine in the nucleus accumbens of mice relative to d-methamphetamine alone. CONCLUSIONS:These results demonstrate that negative modulation of GABAA receptors can produce profound reductions in reward-related effects of a diverse group of drugs that activate the mesolimbic reward pathway through different mechanisms. These data suggest that pharmacological modulation of GABAA receptors may represent a viable pathway for the development of drug abuse pharmacotherapies.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Tracy ME,Banks ML,Shelton KLdoi
10.1007/s00213-015-4155-zsubject
Has Abstractpub_date
2016-02-01 00:00:00pages
715-25issue
4eissn
0033-3158issn
1432-2072pii
10.1007/s00213-015-4155-zjournal_volume
233pub_type
杂志文章abstract::The effects of alcohol on locomotor activity of group- and individually-housed mice were studied using direct ethological observations, including a detailed postural analysis and measures of both locomotion and immobility. Ethanol (0, 0.5, 1.0 and 2.0 g/kg, IP) was given to subjects placed alone in a novel cage, and v...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00464793
更新日期:1984-01-01 00:00:00
abstract:OBJECTIVES:Early onset of heroin use during adolescence might increase chances of later drug addiction. Prior work from our laboratory suggests, however, that adolescent male rats are actually less sensitive than adults to some enduring effects of heroin self-administration. In the present study, we tested two likely c...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-012-2847-1
更新日期:2013-02-01 00:00:00
abstract::After learning a light-cued, go-no go successive discrimination to criterion, male Sprague-Dawley rats received 0, 5, or 10 mg/kg chlordiazepoxide on six performance sessions, followed by two drug-recovery (saline) sessions. Chlordiazepoxide impaired discrimination performance in a dose-dependent manner, with animals ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00652237
更新日期:1986-01-01 00:00:00
abstract:RATIONALE:Prepulse inhibition (PPI) and locomotor activity have been used to investigate the effects of antipsychotic and stimulant drugs and their underlying dopaminergic mechanisms. Whereas D2-like agonists consistently decreased PPI and increased locomotion in rats in previous studies, we recently reported that thes...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0511-3
更新日期:2007-04-01 00:00:00
abstract::Rats treated weekly with cumulative doses (1-100 mg/kg, IP) of naltrexone develop an enhanced sensitivity to the operant response-rate decreasing effect of naltrexone. In the present experiment the pharmacological specificity of that enhanced sensitivity was determined by testing a variety of drugs for cross-sensitivi...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246951
更新日期:1993-01-01 00:00:00
abstract:RATIONALE:Depressed patients robustly exhibit affective biases in emotional processing which are altered by SSRIs and predict clinical outcome. OBJECTIVES:The objective of this study is to investigate whether psilocybin, recently shown to rapidly improve mood in treatment-resistant depression (TRD), alters patients' e...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-017-4754-y
更新日期:2018-02-01 00:00:00
abstract::The effects of intra-amygdala injections of corticotropin-releasing factor (CRF) on memory and exploratory behavior in rats were examined in the present study. Rats with chronically implanted cannulae received intra-amygdala injections of vehicle or CRF at a dose of 0.01, 0.1 or 1.0 micrograms, either immediately afte...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00177566
更新日期:1988-01-01 00:00:00
abstract::Evidence has been provided for impaired neurotransmitter functioning in the brain of elderly subjects. In order to assess central GABAergic transmission, the activity of the hypothalamic GABA system may be investigated by basal growth hormone (GH) response to the GABAergic drug sodium valproate (SV). For this purpose ...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00690918
更新日期:1987-01-01 00:00:00
abstract::The effects of an "aggression"-reducing drug, fluprazine, and an "aggression"-enhancing drug, ethanol, were evaluated in mice using the target biting and resident-intruder paradigms. Under baseline conditions there was a high target biting rate immediately after the delivery of a 2.0 mA tail shock, an intermediate tar...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00217061
更新日期:1987-01-01 00:00:00
abstract::Pigeons were trained to acquire a new 4-response sequence in each session by pecking three keys in a predetermined order. The key color varied for each step under the chained schedule, but there was only one key color under the tandem schedule. Under the reset contingency, incorrect responses produced a reset of the 4...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426823
更新日期:1976-09-29 00:00:00
abstract:BACKGROUND:Marijuana intoxication appears to impair response inhibition, but it is unclear if impaired inhibition and associated brain abnormalities persist after prolonged abstinence among adolescent users. We hypothesized that brain activation during a go/no-go task would show persistent abnormalities in adolescent m...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00213-007-0823-y
更新日期:2007-10-01 00:00:00
abstract:RATIONALE:Kratom is proposed to exhibit therapeutic potential as an opium substitute, but little is known about its dependence-producing profile, particularly of its main psychoactive compound, mitragynine (MG). OBJECTIVES:This study examined the dependence-producing effects of MG using operant-scheduled behaviour in ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-019-05418-6
更新日期:2020-03-01 00:00:00
abstract::Low doses of 8-OH-DPAT (62.5-250 micrograms/kg) were reinforcing in the place preference conditioning procedure, while a higher dose (1 mg/kg) supported a conditioned place aversion. The 5-HT synthesis inhibitor PCPA, and the DA antagonists pimozide and sulpiride, had no effect when administered alone, but abolished t...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244082
更新日期:1991-01-01 00:00:00
abstract::Buprenorphine, a partial mu opioid agonist, is an experimental medication under development for the treatment of opioid dependence as an alternative to methadone maintenance. The present study examined the relationship between level of opioid physical dependence and response to buprenorphine administration as part of ...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF02246290
更新日期:1995-06-01 00:00:00
abstract::The effects of ethanol on locomotor activity and rotarod performance were measured in the rat. Apomorphine (4 mg/kg s.c.) antagonized and pimozide (0.75 - 1.50 mg/kg s.c.) enhanced the effects of a 2 g/kg dose of ethanol on rotarod performance. No such interaction was seen with pentobarbital, 25 mg/kg, a dose sufficie...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00432293
更新日期:1979-01-31 00:00:00
abstract::The four homoeopathic drugs, Gelsemium, Cannabis Indica, Graphites and Agaricus Muscarius, administered orally in 30th and 200th potencies on white rats, enhanced restraint-induced catalepsy in a similar manner to the two standard drugs pilocarpine and haloperidol (IP injection at 5 mg/kg). All the drugs tested differ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00174371
更新日期:1986-01-01 00:00:00
abstract::Cortical and hippocampal EEGs in animal models of schizophrenia were compared to those obtained with psychotomimetics or antipsychotic agents by utilizing power spectral analysis. Models of positive schizophrenic symptoms were created with methamphetamine (MAP) and cocaine, and a model of both negative and positive sy...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050306
更新日期:1997-06-01 00:00:00
abstract:RATIONALE:Coping styles are fundamental characteristics of behavior that affect susceptibility to, and resilience during, mental and physical illness. Shifts from passive to active coping are considered therapeutic goals in many stress-related disorders, but the neural control of coping is poorly understood. Based on e...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-013-3161-2
更新日期:2013-12-01 00:00:00
abstract:RATIONALE:We previously demonstrated that the addition of the selective norepinephrine reuptake inhibitor reboxetine attenuates olanzapine-induced weight gain. Using the same study sample, we also sought to determine whether reboxetine's weight-attenuating effect was accompanied by a beneficial effect on metabolic and ...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-013-3199-1
更新日期:2013-11-01 00:00:00
abstract:RATIONALE:Intermittent social defeat stress can induce neuroadaptations that promote compulsive drug taking. Within the mesocorticolimbic circuit, repeated cocaine administration activates extracellular signal-regulated kinase (ERK). OBJECTIVE:The present experiments examine whether changes in ERK phosphorylation are ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-014-3796-7
更新日期:2015-05-01 00:00:00
abstract:RATIONALE:In Koriat's accessibility model (Koriat, Psychol Rev, 100:609-639, 1993; Koriat, J Exp Psychol Gen, 124:311-333, 1995), when a person fails to recall a required target, he or she can nevertheless provide some partial information about the target. Moreover, individuals are able to provide feeling-of-knowing (F...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-006-0492-2
更新日期:2006-11-01 00:00:00
abstract::The purpose of this review was to establish in vivo apparent pA2 and pKB values for antagonism of the discriminative stimulus effects of benzodiazepine ligands, and to compare these values to those obtained from other behavioral procedures. Articles were chosen from the Medline data base from January 1976 to August 19...
journal_title:Psychopharmacology
pub_type: 杂志文章,meta分析
doi:10.1007/s002130050103
更新日期:1996-11-01 00:00:00
abstract::The discriminative stimulus (DS) effect of apomorphine was investigated in rats trained in a two-lever, food-reinforcement procedure. Rats were given subcutaneous injections of saline or 0.1 mg/kg apomorphine HCl, 15 min before training sessions. The training dose of apomorphine was chosen to activate dopamine autorec...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00690928
更新日期:1987-01-01 00:00:00
abstract::Mice ran in a circular runway. Some received milk at every third circuit in a designated direction, clockwise or counterclockwise, in daily 1000-s sessions. Under control conditions, about 10 times as many circuits were made in the reinforced direction as in the non-reinforced direction. Cocaine (10, 30, 100 microM/kg...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02244125
更新日期:1990-01-01 00:00:00
abstract:RATIONALE:Chronic administration of nicotine in rats results in upregulation of neuronal nicotinic receptors. Upregulation has been proposed to reflect receptor desensitization, which may underlie functional tolerance to nicotine's effects. However, evidence indicates that tolerance and upregulation do not always paral...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130000401
更新日期:2000-05-01 00:00:00
abstract::The performance of healthy volunteer subjects on an auditory latent inhibition (LI) paradigm was assessed following administration of a single oral dose of d-amphetamine or placebo. It was predicted that a low (5 mg), but not a high (10 mg), dose of d-amphetamine would disrupt LI. The prediction was supported with lef...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02245170
更新日期:1992-01-01 00:00:00
abstract::The effects of the selective 5-HT1A agonists 8-OH-DPAT and flesinoxan and the selective 5-HT2 antagonists ritanserin and ketanserin on immobility time in rats bred for predisposition to catalepsy have been studied. Treatment with 8-OH-DPAT as well as flesinoxan caused a marked dose-dependent decrease in immobility tim...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245460
更新日期:1994-02-01 00:00:00
abstract::Tolerance to nicotine occurs in mice after its chronic administration. This tolerance is accompanied by an up-regulation of nicotinic receptors as assessed by the binding of (3H)-nicotine and alpha-(125I)-bungarotoxin (BTX). Past studies (Marks et al. 1983, 1986) have shown that the increase in BTX binding sites is mo...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00212766
更新日期:1988-01-01 00:00:00
abstract:RATIONALE:Alcohol intoxication can dampen negative affective reactions to stressors. Recently, it has been proposed that these acute anxiolytic effects of alcohol may extend to dampening of negative affective reactions to error commission during cognitive control tasks. Nonetheless, empirical verification of this claim...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-020-05619-4
更新日期:2020-11-01 00:00:00
abstract:RATIONALE:The involvement of dopamine neurotransmission in opiate reward remains controversial. OBJECTIVE:To investigate the dopaminergic basis of opiate reward by comparing the effect of systemic injection of the D2/D3 antagonist sulpiride on morphine self-administration (ICSA) into the ventral tegmental area (VTA) o...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-001-0981-2
更新日期:2002-03-01 00:00:00