Abstract：
:Mood disorders, despite the widespread availability of monoamine-based antidepressant treatments, are associated with persistently high rates of disability, together with elevated rates of mortality due to suicide, cardiovascular disease, and other causes. The development of more effective treatments has been hindered by the lack of knowledge about the etiology and pathogenesis of mood disorders. An emerging area of science that promises novel pathways to antidepressant and mood stabilizing therapies surrounds evidence that immune cells and their signaling play a major role in the pathophysiology of major depressive disorder (MDD) and bipolar disorder (BD). Here, we review evidence that the release of neuroactive cytokines, particularly interleukins such as IL-1β, IL-6, and TNF-α, is altered in these disorders and discuss mechanisms such as the ATP-gated ion channel P2X7, through which cytokine signaling can influence neuro-glial interactions. Brain P2X7, an emerging target and antagonism of P2X7 holds promise as a novel mechanism for targeting treatment-resistant depression. We further discuss the role of microglia and astroglia in central neuroinflammation and their interaction with the peripheral immune system We present extant clinical evidence that bolsters the role of neuroinflammation and neuroactive cytokines in mood disorders. To that end, the role of clinical imaging by probing neuroinflammatory markers is also discussed briefly. Finally, we present data using preclinical neuroinflammation models that produce depression-like behaviors in experimental animals to identify neuroinflammatory mechanisms which may aid in novel neuroimmune target identification for the development of exciting pharmacological interventions in mood disorders.
journal_name
Psychopharmacology (Berl)journal_title
Psychopharmacologyauthors
Bhattacharya A,Derecki NC,Lovenberg TW,Drevets WCdoi
10.1007/s00213-016-4214-0subject
Has Abstractpub_date
2016-05-01 00:00:00pages
1623-36issue
9eissn
0033-3158issn
1432-2072pii
10.1007/s00213-016-4214-0journal_volume
233pub_type
杂志文章,评审abstract：RATIONALE:The majority of volumetric magnetic resonance imaging (MRI) studies of the hippocampus in patients with bipolar disorder (BD) show no differences in hippocampal volume between patients and healthy controls. Significant variability, however, exists in the medication status of patients included in these studies...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-007-0906-9
更新日期：2007-12-01 00:00:00
abstract：:Methamphetamine (MAP: 1 and 2 mg/kg SC) and caffeine (CAF: 1, 3, 10 and 30 mg/kg SC) dose-dependently increased ambulation in mice. Repeated administration (5 times at 3 to 4-day intervals) of MAP, but not CAF, induced sensitization to its effect. Furthermore, the mice repeatedly receiving CAF showed no significant ch...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF02245053
更新日期：1994-10-01 00:00:00
abstract：RATIONALE:Although most opioid self-administration research has been conducted with laboratory animals, such research with humans is necessary to answer questions unique to human drug-taking behavior. OBJECTIVE:We investigated the influence of morphine dose and an alternative non-drug reinforcer on choice between morp...
journal_title：Psychopharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/s002130050051
更新日期：2000-02-01 00:00:00
abstract：:Three-hour sessions of differential reinforcement of low-rate behavior (DRL 45-s) in rats were used to investigate alprazolam, caffeine, and their interactions at the onset, peak and disappearance of serum alprazolam, while caffeine level remained constant. The dose-response curve (DRC) method of Pöch permitted an ext...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF02246346
更新日期：1996-07-01 00:00:00
abstract：:The importance of brain noradrenaline synthesis and receptor activation for the hyperkinesia induced by carbidopa plus L-Dopa in reserpine-treated or normal mice was analyzed in four different models. After pretreatment with reserpine and the monoamine oxidase inhibitor nialamide, the hyperkinesia induced by L-Dopa (2...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF00426571
更新日期：1977-11-15 00:00:00
abstract：RATIONALE:The development and validation of animal models of the cognitive impairments of schizophrenia have remained challenging subjects. OBJECTIVE:We review evidence from a series of experiments concerning an animal model that dissociates between the disruption of attentional capacities during acute illness periods...
journal_title：Psychopharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00213-008-1216-6
更新日期：2009-01-01 00:00:00
abstract：:Chronic oral administration of cannabis extract to rats (daily delta 9-tetrahydrocannabinol dose 20 mg/kg) was examined in three experiments for its residual effect on radial-arm maze learning following a 1-month drug-free period. Learning a simple eight-arm maze was significantly impaired in rats treated for either 6...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF00431932
更新日期：1982-01-01 00:00:00
abstract：:7-Hydroxychlorpromazine (7-OHCPZ) has been identified and quantified in CSF from chlorpromazine (CPZ)-treated schizophrenic patients. The level of the metabolite in CSF was similar to that of CPZ. In serum the amount of 7-OHCPZ was about 30% of CPZ. The concentration of 7-OHCPZ in csf was positively and significantly ...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF00432774
更新日期：1982-01-01 00:00:00
abstract：:The benzodiazepines are typified by a profile of side effects which includes drowsiness, ataxia and incoordination. Ro 15-1788, an imidazodiazepine derivative, exhibits marked antagonism of the behavioural and biochemical effects of the benzodiazepines in animals and man. It is devoid of any behavioural activity in an...
journal_title：Psychopharmacology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF00427969
更新日期：1983-01-01 00:00:00
abstract：RATIONALE:Convulsions associated with cocaine toxicity are a serious aspect of cocaine-related emergency room incidents. Seizures can result from a single high dose of cocaine, and evidence is accumulating that correlates repetitive administration of sub-convulsive doses of cocaine with a decreased seizure threshold, a...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s002130050027
更新日期：2000-01-01 00:00:00
abstract：RATIONALE:It has been proposed that brain aldehyde dehydrogenase (ALDH) plays a role in the modulation of some psychopharmacological effects of ethanol. Diethyldithiocarbamate (DDTC), an ALDH inhibitor, elevates blood acetaldehyde levels in the presence of ethanol. Concurrent administration with 4-methylpyrazole (4-MP)...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-001-0991-0
更新日期：2002-04-01 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：:In a series of experiments, rats received the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801 and measures were made of motor behavior, spatial navigation in a swimming pool, and electroencephalographic (EEG) activity. High doses (0.25-10 mg/kg IV) produced somnolence and akinesia, impaired food consumpti...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF00441949
更新日期：1989-01-01 00:00:00
abstract：:The increasing interest in subjective well-being and quality of life of schizophrenic patients represents a conceptual shift in therapeutic outcome criteria. Symptom reduction alone was the most essential outcome parameter for a long time; with the development of atypical antipsychotics more ambitious success criteria...
journal_title：Psychopharmacology
pub_type： 杂志文章,评审
doi：10.1007/s00213-002-1052-z
更新日期：2002-06-01 00:00:00
abstract：RATIONALE:Recently, we showed that 2-bromoterguride acted as a dopamine D2 receptor partial agonist, a serotonin 5-HT2A and α2C-adrenergic receptor antagonist, and exhibited antidopaminergic efficacy in amphetamine-induced locomotion (AIL) in rats without inducing catalepsy. OBJECTIVE:To extend our knowledge on the an...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-016-4356-0
更新日期：2016-08-01 00:00:00
abstract：:MA rats, bred for greater motor impairment following subhypnotic doses of ethanol, were found to be more sensitive to the hypnotic effects of phenobarbital and chloral hydrate than were LA rats. In addition, the previously reported finding of a difference between the two lines of rats in duration of loss of righting r...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF00426674
更新日期：1979-02-28 00:00:00
abstract：:Benzodiazepines and other compounds which act at benzodiazepine binding sites have been shown previously to attenuate the acquisition of conditioned fear in rodents when administered before the acquisition session, an effect which may parallel the disruption of human memory produced by anxiolytics and sedatives. Such ...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF00181243
更新日期：1986-01-01 00:00:00
abstract：RATIONALE:Pairing rewarding outcomes with audiovisual cues in simulated gambling games increases risky choice in both humans and rats. However, the cognitive mechanism through which this sensory enhancement biases decision-making is unknown. OBJECTIVES:To assess the computational mechanisms that promote risky choice d...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-019-05308-x
更新日期：2019-08-01 00:00:00
abstract：:A number of clinically used benzodiazepines were tested for their effectiveness in blocking muscimol-induced myoclonic jerks in mice. Their ED50 values were determined from their dose-response curves. These data gave the following relative potencies with respect to diazepam: diazepam = 1, medazepam = 0.24, oxazepam = ...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF00432441
更新日期：1981-01-01 00:00:00
abstract：RATIONALE:Emerging evidence from agonist-antagonist studies suggests a role for the dopamine D(3) receptor subtype in the regulation of PPI in animals, but such evidence is lacking for human subjects. OBJECTIVES:This study examines the effect of the preferential D(3) agonist ropinirole on PPI in humans. METHODS:PPI w...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-007-0843-7
更新日期：2007-10-01 00:00:00
abstract：RATIONALE:The exact role of delta opioid receptors in drug-induced conditioned place preference (CPP) remains debated. Under classical experimental conditions, morphine-induced CPP is decreased in mice lacking delta opioid receptors (Oprd1 (-/-)). Morphine self-administration, however, is maintained, suggesting that dr...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-012-2693-1
更新日期：2012-09-01 00:00:00
abstract：BACKGROUND:The serotonin (5-HT) deficiency hypothesis of aggression is being seriously challenged by pharmacological data showing robust anti-aggressive effects of 5-HT1A receptor agonists in dose ranges that concomitantly inhibit 5-HT neurotransmission. Hence, an adequate interpretation of the role of 5-HT activity in...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-015-4173-x
更新日期：2016-03-01 00:00:00
abstract：:In order to study trends in smoking withdrawal symptoms, 35 participants in a smoking cessation clinic completed four questionnaires daily for 2 weeks. The questionnaire dealt with a variety of symptoms which a factor analysis showed could be grouped into four factors: stimulation, desire to smoke, and physical and ps...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/BF00634151
更新日期：1976-10-20 00:00:00
abstract：RATIONALE:Both central serotonergic and nicotinic systems play important roles in a variety of neurobehavioral functions; however, the interactions of these two systems have not been fully characterized. The current study served to determine the impact of a relatively selective 5-HT2A receptor antagonist, ketanserin, o...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-004-2060-y
更新日期：2005-05-01 00:00:00
abstract：RATIONALE:Acute tryptophan depletion (ATD) transiently lowers central serotonin levels and can induce depressive mood states and cognitive defects. Previous studies have shown that ATD impairs object recognition in rats. OBJECTIVES:As individual differences exist in central serotonin neurotransmission, the impact of A...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-008-1201-0
更新日期：2008-10-01 00:00:00
abstract：RATIONALE:Subthreshold smokers (who smoke < or =5 cigarettes/day) experience withdrawal symptoms, yet they smoke less than is required to maintain serum nicotine levels. OBJECTIVES:For study 1, our aim was to determine (1) if adult subthreshold smokers report withdrawal symptoms; (2) how they rate symptom severity; (3...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-006-0497-x
更新日期：2006-10-01 00:00:00
abstract：RATIONALE:3,4-methylenedioxymethamphetamine (MDMA, ecstasy) produces an acute release of 5-HT in the brain, together with increased locomotion and hyperthermia. OBJECTIVE:This study examined whether the acute functional changes of locomotor activity and body temperature are related to enhanced 5-HT release induced by ...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-010-1921-9
更新日期：2011-02-01 00:00:00
abstract：RATIONALE:The neuronal actions of methamphetamine (MA) include an increase in extracellular levels of monoamines, presumably via reverse transport involving the monoamine transporters. This action is thought to play an important role in the effects of MA. Therefore, in the present experiment, it was hypothesized that a...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s002130000602
更新日期：2000-12-01 00:00:00
abstract：RATIONALE:Caffeine and the adenosine A(1) and A(2A) receptor antagonist CGS15943 produce many behavioral effects that are similar to those produced by classic stimulant drugs (e.g. cocaine and amphetamines). OBJECTIVES:The current study evaluated whether CGS15943 would maintain self-administration and reinstate exting...
journal_title：Psychopharmacology
pub_type： 杂志文章
doi：10.1007/s00213-003-1410-5
更新日期：2003-07-01 00:00:00
abstract：:Cigarette smokers have a wide variety of "tar" and nicotine yields to choose from in the current market, ranging from 0.5 mg "tar" and less than 0.05 mg nicotine to 27 mg "tar" and 1.8 mg nicotine by the Federal Trade Commission (FTC) method. To understand better the relationship between FTC nicotine yields and actual...
journal_title：Psychopharmacology
pub_type： 临床试验,杂志文章
doi：10.1007/BF02246082
更新日期：1995-11-01 00:00:00
