Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033377 (prolapse)
 11,717 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Drug withdrawal is an integral part of most types of dependence and, to a large extent, opiate withdrawal has been considered the prototypic, classic measure of opiate dependence. The opiate withdrawal syndrome is characterized by multiple behavioral and physiological signs such as behavioral activation, ptosis, diarrhea, 'wet dog' shakes and motivational dysfunction, which may be represented in the CNS at multiple sites. It seems that the activating effects associated with the opiate withdrawal syndrome may be mediated by the nucleus locus coeruleus. Other signs such as wet dog shakes may involve sites in the hypothalamus important for temperature regulation. Certain other signs such as diarrhea and lacrimation may be dependent on peripheral opiate receptors. The motivational aspects of opiate withdrawal as demonstrated by the aversive stimulus effects or negative reinforcing effects (e.g. disrupted lever-pressing for food and place aversions) may involve those elements of the nucleus accumbens that are known to be important for the acute reinforcing effects of opiates in nondependent rats. Evidence exists at the cellular and molecular level for both 'within-system' and 'between-system' adaptations to dependence. Elucidation of the neural networks, cellular mechanisms and molecular elements involved in opiate withdrawal may provide not only a model for our understanding of the adaptive processes associated with drug dependence but also of those associated with other chronic insults to CNS function.
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PMID:Neural substrates of opiate withdrawal. 137 26

In primates, CB(1) cannabinoid receptor agonists produce sedation and psychomotor slowing, in contrast to behavioral stimulation produced by high doses of dopamine receptor agonists. To investigate whether dopamine agonists attenuate the sedative effects of a cannabinoid agonist in monkeys, we compared the effects of D(1) or D(2) dopamine receptor agonists on spontaneous behavior in three to six cynomolgus monkeys (Macaca fasicularis) alone and after administration of a low dose of the CB(1) agonist levonantradol. Alone, the CB(1) cannabinoid receptor agonist levonantradol (0.01-0. 3 mg/kg) induced sedation, ptosis, and decreased locomotor and general activity. Alone, D(2)-type dopamine agonists quinelorane (0. 001-1.0 mg/kg; n = 4) or pergolide (0.01-1.0 mg/kg) or a D(1) dopamine agonist 6-chloro-7,8-dihydroxy-1-phenyl-2,3,4, 5-tetrahydro-3-allyl-[1H]-3-benzazepine (0.3-3.0 mg/kg) produced either no effect or promoted hyperactivity. Thirty minutes after administration of a threshold dose of levonantradol (0.03 mg/kg), D(2)-type agonists, but not the D(1) agonist, precipitated marked sedation, ptosis, and decreased general activity and locomotor activity. These data inducate the following: 1) D(2,) but not D(1) dopamine agonists, potentiate sedation in monkeys treated with a CB(1) cannabinoid agonist, at doses of agonists that alone do not produce sedation; 2) the threshold dose for cannabinoid-induced sedation is reduced by D(2) agonists, but not by a D(1) dopamine agonist, differentiating D(1) and D(2) dopamine receptor linkage to cannabinoid receptors; and 3) modulation of D(2) dopamine receptor activity by a nonsedating dose of a cannabinoid agonist has implications for the pathophysiology and treatment of dopamine-related neuropsychiatric disorders and drug addiction. Cannabinoid agonists and D(2) dopamine agonists should be combined with caution.
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PMID:D(2), but not D(1) dopamine receptor agonists potentiate cannabinoid-induced sedation in nonhuman primates. 1068 9

Glutamate receptors are implicated in the development and expression of drug dependence. Substantial experimental evidence suggests that antagonists acting at the N-methyl-D-aspartate (NMDA) subtype of glutamate receptors attenuate the severity of opioid withdrawal. However, it is less clear whether opioid withdrawal can be potentiated by agonists of glutamate receptors. The present study evaluated the behavioural effects of various agonists of glutamate receptors, as well as a nitric oxide (NO) donor, in morphine-dependent rats trained to discriminate 0.1 mg/kg of naloxone from saline. None of the following drugs produced appreciable levels of naloxone-like responding (substitution tests) or potentiated the discriminative stimulus effects of naloxone: NMDA (3-56 mg/kg), glycine (100-1000 mg/kg), glutamate (1000-3000 mg/kg), kainate (0.3-3 mg/kg), isosorbide dinitrate (30-300 mg/kg). Nevertheless, expression of some morphine withdrawal-like somatic and behavioural signs ('wet-dog'-like shaking, scream on touch, ptosis, tremor, chewing, weight loss) was facilitated by NMDA, glycine, and isosorbide dinitrate. These results suggest that, compared to somatic symptoms, subjective effects of opioid withdrawal (as reflected by discriminative stimulus effects) are not mimicked by direct activation of glutamate receptors.
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PMID:Behavioural effects of glutamate receptor agonists in morphine-dependent rats. 1078 Aug 4