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)

The influence of the D1 antagonist SCH 23390 on the motivational properties of rewarding (morphine, nicotine and diazepam) and aversive (naloxone, phencyclidine and picrotoxin) drugs was studied in the rat in a two-compartment place-conditioning paradigm, which included a pre-conditioning test for spontaneous place-preference. The specific D1 dopamine-receptor antagonist SCH 23390 (0.05 mg/kg SC), paired with both compartments or, separately, with the preferred or with the non-preferred compartment, failed to affect the spontaneous unconditioned preference of the animal. Pairing of morphine (1.0 mg/kg SC), nicotine (0.6 mg/kg SC) or diazepam (1.0 mg/kg IP) with the less preferred compartment induced significant preference for that compartment. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments completely blocked the place-preference induced by morphine, nicotine and diazepam. Naloxone (0.8 mg/kg SC), phencyclidine (2.5 mg/kg SC) or picrotoxin (2.0 mg/kg IP) paired with the preferred compartment elicited place-aversion. Pairing of SCH 23390 (0.05 mg/kg SC) with both compartments abolished also the place-aversion induced by naloxone, phencyclidine and picrotoxin. The results indicate that blockade of dopamine transmission blocks the motivational properties of rewarding as well as aversive stimuli. It is suggested that neuroleptics rather than simply blocking the rewarding impact of positive reinforcers (anhedonia, lack of pleasure) exert a more general influence on conditioned behaviour by blocking the affective impact of negative as well as positive reinforcers (apathy, lack of motivation).
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PMID:SCH 23390 blocks drug-conditioned place-preference and place-aversion: anhedonia (lack of reward) or apathy (lack of motivation) after dopamine-receptor blockade? 257 27

1. This work was undertaken in order to study whether the opioid system is involved in the modulation of the behaviors induced by two agonists of the dopaminergic system, amphetamine and apomorphine in adult cats. 2. Naloxone, an antagonist of the mu, delta and kappa opioid receptors was administered to twelve female mongrel cats; 0.5, 1.0 and 2.0 mg/kg s.c. were injected in order to analyse its own effect of naloxone. This drug produced NREMs behavior and accordingly the cat showed an overall decrease of its activities. 3. Amphetamine (2.5 mg/kg s.c.) and apomorphine (2.0 mg/kg s.c.) were injected before and after naloxone administration (2.0 mg/kg s.c.), in separate sessions. 4. The behaviors recorded were compared. Some of the behaviors showed modifications both with amphetamine (inappetence was increased and locomotion decreased) and apomorphine (indifference and inappetence increased; locomotion and olfaction decreased). 5. These changes were considered as consequence of the NREMs behavior induced by naloxone and not as a result of a modulation by the opioid system of the activation of the dopaminergic system elicited by amphetamine and apomorphine. Regarding the mechanism of NREMs induced by naloxone probably the dopaminergic, noradrenergic and GABAergic systems may be involved.
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PMID:Effects of naloxone on the behaviors evoked by amphetamine and apomorphine in adult cats. 762 98

The relationship between naloxone-plasma concentrations and their effects on mood and endocrine function was studied. Ten healthy volunteers received 1.0 mg/kg i.v. naloxone or placebo following a randomized double-blind design. Effects on mood, determined by a visual analogue scale and luteinizing hormone (LH) and naloxone-plasma concentrations were measured at selected times. Naloxone induced significant effects on confusion, bewilderment and indifference, and an increment in LH levels. The timecourse of the responses on confusion and bewilderment was similar to that of naloxone-plasma concentration, suggesting that these effects are directly related to the action of naloxone on its receptors. Responses for indifference and LH, however, exhibited a delayed onset. This delay could be due to an indirect action, i.e. to the participation of additional physiological mechanisms in a cascade-like manner. The results show that analysis of the concentration-effect relationship can be a useful tool for understanding naloxone effects on mood and endocrine function.
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PMID:The use of the plasma concentration-effect relationship as a tool for the study of the mechanism of action of naloxone effects on mood and endocrine function. 944 26