Abstract:
BACKGROUND:The general premise that receptor theory provides a useful framework for understanding the behavioral effects of psychoactive drugs has been a central tenet of behavioral pharmacology. OBJECTIVES:The purpose of this review is to reiterate this basic theme and, in particular, the proposition that current concepts of pharmacological efficacy can be effectively used to examine behavioral effects of drugs with abuse or dependence potential in a way that contributes to the discovery of drugs to treat drug dependence. EXPERIMENTAL DATA:The review begins by briefly introducing the concept of efficacy and follows with several illustrations of how our current understanding of efficacy can be used to address important research questions in drug discovery. In the first, the likelihood of developing novel opioid analgesics with reduced abuse potential is addressed by considering the different efficacy requirements for the discriminative-stimulus and antinociceptive effects of mu-opioids. From a pharmacologically different perspective within drug abuse research, the review continues with an exposition of efficacy-related differences in the behavioral effects of dopamine D1 agonists and how such differences might be exploited in different medications strategies for treating cocaine dependence. The principles of pharmacological efficacy also have come to guide the development of novel GABAA-related antianxiety medications, and this is illustrated in a discussion of the utility of low-efficacy agonists in the treatment of benzodiazepine dependence. The second half of the paper provides counterpoint to the several examples of how principles of efficacy can be applied in drug discovery. The counterpoint includes, first, a critical evaluation of how the concept of efficacy has been applied in the development of monoamine transport inhibitors as anti-cocaine medications and, in particular, the difficulties this may pose for data analysis. The review ends with a discussion of efficacy-based analysis in drug discrimination research and illustrates some of the obstacles that may be encountered in pharmacologically classifying drugs on this basis. CONCLUSIONS:Ample evidence indicates that many receptor systems can be activated in a graded manner and that principles of efficacy can be judiciously applied to understand and exploit the behavioral effects of drugs that result from such graded activation. However, as cautioned in the last sections, the misapplication of pharmacological concepts in behavioral studies of drugs may obscure their behavioral pharmacology and potentially confound drug discovery.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Bergman J,France CP,Holtzman SG,Katz JL,Koek W,Stephens DNdoi
10.1007/s002130000567subject
Has Abstractpub_date
2000-12-01 00:00:00pages
67-84issue
1eissn
0033-3158issn
1432-2072journal_volume
153pub_type
杂志文章,评审abstract:OBJECTIVE:The pharmacological profile of escitalopram, the S-(+)-enantiomer of citalopram, was studied and compared with citalopram and the R-(-)-enantiomer, R-citalopram. METHODS:Inhibition of the serotonin transporter (5-HTT) was studied in COS-1 cells expressing the human 5-HTT (h-5-HTT) and in rat brain synaptosom...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-002-1364-z
更新日期:2003-06-01 00:00:00
abstract::The effects of monoamine oxidase inhibitors (MAOIs) that selectively inhibit the MAO-A or MAO-B forms of MAO were studied in rats performing under a differential-reinforcement-of-low-rate 72-s (DRL 72-s) schedule of reinforcement. Clorgyline and CGP11'305A, irreversible and reversible MAO-A inhibitors, respectively, i...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00177554
更新日期:1988-01-01 00:00:00
abstract::Two methods were used to assess nicotine-induced antinociception: tail withdrawal from a hot water bath and hind paw withdrawal from a hotplate. Nicotine doses which produced 75-80% maximum response were 0.75 mg/kg (free base) for tail withdrawal and 0.35 mg/kg for paw withdrawal. The peripheral blocker chlorisondamin...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02246552
更新日期:1995-12-01 00:00:00
abstract:RATIONALE:A sensitized dopamine system may be linked to the genesis of psychotic symptoms in schizophrenia. Following withdrawal from amphetamine exposures, psychotic-like traits have been robustly demonstrated, but the presence of cognitive/mnemonic deficits remains uncertain. METHODS:Adult male Lewis and Fischer rat...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-009-1514-7
更新日期:2009-11-01 00:00:00
abstract::Single oral and intramuscular (i.m.) doses of imipramine (IMI) were administered to four normal males. Serum and urine concentrations of IMI, desipramine (DMI) and their unconjugated 2-hydroxy metabolites were measured by high-pressure liquid chromatography (HPLC). Urinary conjugated 2-hydroxy metabolites were also me...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/BF00427676
更新日期:1984-01-01 00:00:00
abstract::The present report investigated several parametric and pharmacological aspects of the enhanced self-grooming behavior of rats following systemic administration of the selective D1 dopamine (DA) receptor agonist SKF 38393. The amount of time that rats spent grooming themselves was measured continuously for 30 min follo...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245478
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND:This laboratory study investigated the mechanisms by which the opioid antagonist, naltrexone, reduces the risk of relapse to heavy drinking in individuals with alcohol dependence. METHODS:Eighteen alcohol-dependent, non-treatment-seeking volunteers were randomized to 50 mg naltrexone or placebo for 6 days a...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/s002130100919
更新日期:2002-02-01 00:00:00
abstract::Food reward has been associated with activation of noradrenergic mechanisms in the brain. Using rats trained to press a lever for food reward, we have investigated the effects of 6-hydroxydopamine lesions, which severly depleted hypothalamic noradrenaline, on the willingness of the rats to press the lever for food rew...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00427343
更新日期:1979-06-28 00:00:00
abstract:RATIONALE:Nicotine and nicotinic agonists have been shown to improve attentional function. Nicotinic receptors are easily desensitized, and all nicotinic agonists are also desensitizing agents. Although both receptor activation and desensitization are components of the mechanism that mediates the overall effects of nic...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-012-2895-6
更新日期:2013-03-01 00:00:00
abstract::In the present pilot study, an attempt was made to shape and maintain cigarette smoking behavior in rhesus monkeys both with and without the simultaneous use of other reinforcers. Initially, 14 monkeys were trained to suck air and puff on cigarettes using sweetened liquid reinforcer. After smoking had been established...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00431644
更新日期:1981-01-01 00:00:00
abstract::Doses of eight phenylethylamines were substituted for cocaine on a drug-maintained behavior baseline in baboons. Intravenous infusions of drug were contingent upon completion of 160 lever presses (a 160-response fixed-ratio schedule; FR 160). A 3-h time-out period followed each infusion, permitting a maximum of 8 infu...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00426841
更新日期:1976-11-24 00:00:00
abstract::Oxytocin plays an important role in the regulation of normal cognitive functions and behaviors, which are disturbed in schizophrenia. Several studies suggest that oxytocinergic function is abnormal in schizophrenia patients. Thus, oxytocin may be involved in the pathophysiology associated with this disorder. This stud...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050811
更新日期:1999-01-01 00:00:00
abstract:RATIONALE:Gabolysat PC60 is a fish protein hydrolysate with anxiolytic properties commonly used as a nutritional supplement. OBJECTIVE:The diazepam-like effects of PC60 on stress responsiveness of the rat pituitary-adrenal system and on sympathoadrenal activity were studied. METHODS:The activity of the pituitary-adre...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002139900338
更新日期:2000-03-01 00:00:00
abstract::Depression is common in patients with senile dementia of the Alzheimer type (SDAT) and may precede the onset of the dementia; the underlying biological and neurotransmitter mechanisms may be common to both diseases, so far as norepinephrine lesions are concerned. The major routes of metabolism of amines in the brain u...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF02246259
更新日期:1992-01-01 00:00:00
abstract:RATIONALE:Caffeine is commonly believed to offset the acute effects of alcohol, but some evidence suggests that cognitive processes remain impaired when caffeine and alcohol are coadministered. OBJECTIVES:No previous study has investigated the separate and joint effects of alcohol and caffeine on conflict monitoring a...
journal_title:Psychopharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00213-016-4208-y
更新日期:2016-04-01 00:00:00
abstract:RATIONALE:Repeated administration of psychoactive drugs results in a progressive enhancement of the behavioral effects of these compounds, a phenomenon termed sensitization. OBJECTIVE:We tested whether repeated administration of the non-competitive NMDA receptor antagonist dizocilpine (MK-801) induces sensitization of...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130100776
更新日期:2001-07-01 00:00:00
abstract::Twelve healthy male volunteers took part in a double-blind randomised cross-over study composed of three treatment sessions: remoxipride 100 mg; remoxipride 100 mg plus biperiden 4 mg; and biperiden 4 mg. Plasma and urine concentrations of remoxipride and biperiden, plasma prolactin levels, salivary flow and adverse e...
journal_title:Psychopharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF02257403
更新日期:1993-01-01 00:00:00
abstract:RATIONALE:Understanding factors contributing to individual differences in vulnerability to opioid addiction is essential for developing more effective preventions and treatments, yet few reliable behavioral predictors of subsequent opioid self-administration have been identified in rodents. Sensitivity to the acute eff...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-020-05532-w
更新日期:2020-08-01 00:00:00
abstract::2Beta-propanoyl-3beta-(4-tolyl)-tropane (PTT) is a cocaine analog which has been shown in rhesus monkeys to have cocaine-like discriminative stimulus effects and a long duration of action (>8 h), yet does not function as a reinforcer when substituted for cocaine in monkeys responding under a fixed-interval 5-min sched...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s002130050549
更新日期:1998-03-01 00:00:00
abstract::The acute effect of ethanol upon the NSD (normalized slope descriptors) or Hjorth parameters of EEG were analyzed in 11 students. The maximal blood-alcohol concentration ranged from 1.0--1.7 mg/l. The activity (mean amplitude) increased and the complexity (frequency spread) decreased significantly as a function of tim...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00429184
更新日期:1978-12-15 00:00:00
abstract:RATIONALE:Clinical observations have shown that pain sensitivity is altered in some schizophrenic patients. OBJECTIVES:To study alterations in pain sensitivity, the ketamine model in schizophrenia research was employed. MATERIALS AND METHODS:Rats were subchronically injected with the dissociative anaesthetic ketamine...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0557-2
更新日期:2006-12-01 00:00:00
abstract:RATIONALE:Fluoxetine (Prozac®) is the most frequently prescribed drug to battle depression in pregnant women, but its safety in the unborn child has not yet been established. Fluoxetine, a selective serotonin reuptake inhibitor, crosses the placenta, leading to increased extracellular serotonin levels and potentially n...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-011-2299-z
更新日期:2011-10-01 00:00:00
abstract:RATIONALE:Calcineurin is a protein regulating cytokine expression in T lymphocytes and calcineurin inhibitors such as cyclosporine A (CsA) are widely used for immunosuppressive therapy. It also plays a functional role in distinct neuronal processes in the central nervous system. Disturbed information processing as seen...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-020-05751-1
更新日期:2020-12-21 00:00:00
abstract:RATIONALE:Attention-deficit/hyperactivity disorder (ADHD) is thought to involve hypofunctional catecholamine systems in the striatum, nucleus accumbens, and prefrontal cortex (PFC); however, recent clinical evidence has implicated glutamate dysfunction in the pathophysiology of ADHD. Recent studies show that increased ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-014-3479-4
更新日期:2014-08-01 00:00:00
abstract::A study was performed on the effect of ethanol on the basal and K+-evoked efflux of endogenous GABA from rat hypothalamic fragments. The amount of GABA present in the medium and in the tissue was measured by radioreceptor assay. In vitro addition of ethanol (50 and 100 mM) enhanced the K+-evoked efflux of GABA in a Ca...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00181959
更新日期:1988-01-01 00:00:00
abstract::To test the Pavlovian conditioning model of alcohol tolerance, two groups of eight male social drinkers each received five administrations of alcohol and five administrations of an equal volume of tonic each, on an alternating basis, during the initial 10-session tolerance development phase of the study. Group 1 recei...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00310519
更新日期:1986-01-01 00:00:00
abstract::The opioid antagonist effects of systemically administered nor-binaltorphimine (nor-BNI) were evaluated against the kappa agonists CI-977, U69,593, U50,488, ethylketocyclazocine (EKC), Mr2034 and bremazocine, the mu agonist morphine and the alkaloid delta agonist BW-373U86 in the acetic acid-induced writhing assay in ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF02245071
更新日期:1994-07-01 00:00:00
abstract:RATIONALE:Rats selectively bred for high saccharin (HiS) intake consume more alcohol and acquire intravenous (i.v.) cocaine self-administration more rapidly than their low saccharin (LoS)-consuming counterparts. The present experiment was designed to determine whether HiS and LoS rats differed in other aspects of drug ...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/s00213-006-0600-3
更新日期:2007-02-01 00:00:00
abstract::It is commonly believed that repeated exposures diminish the pleasurable effects of drugs and hence that pleasure must have only a minor role in addiction. In six experiments with rats, repeated exposures to amphetamine, morphine, or cocaine were found to enhance the drug-induced rewarding effect as measured by condit...
journal_title:Psychopharmacology
pub_type: 杂志文章
doi:10.1007/BF00451687
更新日期:1989-01-01 00:00:00
abstract::The behavioral effects of the benzodiazepine (BZP)-receptor partial inverse agonists, beta-CCE and FG 7142, are reviewed and the claim that these compounds possess "anxiogenic" properties is examined. Results obtained from human studies and global observations in animals, as well as those from experiments on aggressio...
journal_title:Psychopharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00212837
更新日期:1988-01-01 00:00:00