Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0085632 (apathy)
 4,089 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Seven patients with refractory seizure disorders and neuropsychiatric symptoms believed secondary to felbamate are presented. Five were on concomitant valproic acid (and other agents). Anergia, apathy, bradyphrenia, and increased irritability were prominent. One patient on felbamate monotherapy had a new-onset psychosis. Felbamate's NMDA receptor antagonism and GABA potentiation (perhaps enhanced by valproic acid use) are discussed as possible mechanisms of these side effects.
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PMID:Neuropsychiatric side effects related to treatment with felbamate. 901 38

Organisms often make effort-related choices based upon assessments of motivational value and work requirements. Nucleus accumbens dopamine is a critical component of the brain circuitry regulating work output in reinforcement-seeking behavior. Rats with accumbens dopamine depletions reallocate their instrumental behavior away from food-reinforced tasks that have high response requirements, and instead they select a less-effortful type of food-seeking behavior. The ventral pallidum is a brain area that receives substantial GABAergic input from nucleus accumbens. It was hypothesized that stimulation of GABA(A) receptors in the ventral pallidum would result in behavioral effects that resemble those produced by interference with accumbens dopamine transmission. The present studies employed a concurrent choice lever pressing/chow intake procedure; with this task, interference with accumbens dopamine transmission shifts choice behavior such that lever pressing for food is decreased but chow intake is increased. In the present experiments, infusions of the GABA(A) agonist muscimol (5.0-10.0 ng) into the ventral pallidum decreased lever pressing for preferred food, but increased consumption of the less preferred chow. In contrast, ventral pallidal infusions of muscimol (10.0 ng) had no significant effect on preference for the palatable food in free-feeding choice tests. Furthermore, injections of muscimol into a control site dorsal to the ventral pallidum produced no significant effects on lever pressing and chow intake. These data indicate that stimulation of GABA receptors in ventral pallidum produces behavioral effects similar to those produced by accumbens dopamine depletions. Ventral pallidum appears to be a component of the brain circuitry regulating response allocation and effort-related choice behavior, and may act to convey information from nucleus accumbens to other parts of this circuitry. This research may have implications for understanding the brain mechanisms involved in energy-related psychiatric dysfunctions such as psychomotor retardation in depression, anergia, and apathy.
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PMID:Forebrain circuitry involved in effort-related choice: Injections of the GABAA agonist muscimol into ventral pallidum alter response allocation in food-seeking behavior. 1827 91

Baclofen, a GABA-B receptor agonist, is a promising treatment for alcohol use disorder (AUD). Its mechanism of action in this condition is unknown. GABA-B receptors interact with many biological systems potentially involved in AUD, including transduction pathways and neurotransmitter systems. Preclinical studies have shown that GABA-B receptors are involved in memory storage and retrieval, reward, motivation, mood and anxiety; neuroimaging studies in humans show that baclofen produces region-specific alterations in cerebral activity; GABA-B receptor activation may have neuroprotective effects; baclofen also has anti-inflammatory properties that may be of interest in the context of addiction. However, none of these biological effects fully explain the mechanism of action of baclofen in AUD. Data from clinical studies have provided a certain number of elements which may be useful for the comprehension of its mechanism of action: baclofen typically induces a state of indifference toward alcohol; the effective dose of baclofen in AUD is extremely variable from one patient to another; higher treatment doses correlate with the severity of the addiction; many of the side effects of baclofen resemble those of alcohol, raising the possibility that baclofen acts as a substitution drug; usually, however, there is no tolerance to the effects of baclofen during long-term AUD treatment. In the present article, the biological effects of baclofen are reviewed in the light of its clinical effects in AUD, assuming that, in many instances, clinical effects can be reliable indicators of underlying biological processes. In conclusion, it is proposed that baclofen may suppress the Pavlovian association between cues and rewards through an action in a critical part of the dopaminergic network (the amygdala), thereby normalizing the functional connectivity in the reward network. It is also proposed that this action of baclofen is made possible by the fact that baclofen and alcohol act on similar brain systems in certain regions of the brain.
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PMID:A Review of the Potential Mechanisms of Action of Baclofen in Alcohol Use Disorder. 3045 46

The lateral hypothalamus (LH) is critical for generating context-appropriate actions. LH deficits uncouple behaviour and motor control from internal and external environmental influences. Non-specific LH lesions produce apathy, akinesia, and weight loss. Targeted impairments of brain-wide-projecting LH cells, such as orexin or GABA neurons, result in context-inappropriate arousal and motor control, and pathological eating. Generating timely adaptive actions requires timely updating of neural representations of context. Here we review how activity patterns of different LH neurons represent rapid external events on subsecond timescales. We discuss experience-dependent plasticity of these representations and their impact on wider neural processing and sensorimotor control, with a focus on LH orexin neurons. We highlight key questions, such as neural origins of rapid LH dynamics, and whether LH encodes sensory or motor activity. Real-time monitoring of fast LH dynamics during learning will be vital for understanding the elusive algorithms that allow the brain to combine fast and slow variables to guide actions.
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PMID:Fast sensory representations in the lateral hypothalamus and their roles in brain function. 3244 12