Supersensitivity of brain opiate receptor subtypes after chronic naltrexone treatment

Tempel, Ann; Zukin, R. Suzanne; Gardner, Eliot L.

doi:10.1016/0024-3205(82)90391-5

Cited by 87 publications

(22 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interactions between mechanisms mediated by the D1 and D2 subclasses of dopamine receptors [26], or alterations in other transmitter systems may be contributory 127). The time course for the remission of fluctuations in motor function during continuous levodopa treatment and their relapse following resumption of intermittent oral administration is consistent with the time course of the development of receptor downregulation and upregulation and receptor regeneration 123, [28][29][30]. Failure of the dose-response slope to decline may be due to either permanent alterations in postsynaptic mechanisms secondary to chronic denervation or an insufficient treatment duration to influence this measure.…”

Section: Discussionmentioning

confidence: 68%

Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease

Mouradian

Heuser

Baronti

et al. 1990

Annals of Neurology

223

View full text Add to dashboard Cite

The management of fluctuations in motor function complicating advanced Parkinson's disease with continuously administered dopaminomimetics was studied in 12 patients. In response to 7 to 12 days of round-the-clock intravenous infusions of levodopa, fluctuations in motor performance gradually diminished, ultimately by more than 40%. The beneficial effect persisted for about 6 days after withdrawal of continuous parenteral treatment and resumption of standard oral therapy. Clinical improvement was associated with changes in several pharmacological indices: Acute dose-response studies of intravenous levodopa showed a shift of the curve to the right in the immediate postinfusion phase compared to preinfusion studies; the therapeutic index improved significantly as patients demonstrated about 76% increased beneficial antiparkinsonian response with an equal degree of toxic dyskinetic effects; and the duration of action of levodopa was prolonged by 30%. These results suggest that changes in central dopaminergic mechanisms contributing to motor complications in advanced Parkinson's disease can be modified by procedures that provide continuous dopamine replacement. Presumably these modifications underlie the gradual amelioration of motor fluctuations over several days of round-the-clock therapy. Results of the present study also suggest potential deleterious effects of chronic intermittent oral treatment in the development of motor complications and thus support the role of long-term, continuous administration of dopaminomimetics.

show abstract

Section: Discussionmentioning

confidence: 68%

Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease

Mouradian

Heuser

Baronti

et al. 1990

Annals of Neurology

223

View full text Add to dashboard Cite

show abstract

“…The expression of κ-opioid receptors was nearly unchanged (9 and 1% in the VTA and NAcc, respectively) [24]. This up-regulation of opioid receptors has been shown to accompany supersensitivity to opioid agonists and is an indication of their functional relevance [48]. Moreover, repeated treatment with AMPH or METH was found to increase not only the mRNA levels of μ-opioid receptors in the VTA and NAcc [27] but also the dopamine releasing effects of μ-opioid receptor agonist [55].…”

Section: Discussionmentioning

confidence: 88%

Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone

Chiu

2005

Brain Research Bulletin

View full text Add to dashboard Cite

Repeated intermittent exposure to psychostimulants was found to produce behavioral sensitization. The present study was designed to establish a mouse model and by which to investigate whether opioidergic system plays a role in methamphetamine-induced behavioral sensitization. Mice injected with 2.5 mg/kg of methamphetamine once a day for 7 consecutive days showed behavioral sensitization after challenge with 0.3125 mg/kg of the drug on day 11, whereas mice injected with a lower daily dose (1.25 mg/kg) did not. Mice received daily injections with either 1.25 or 2.5 mg/kg of methamphetamine showed behavioral sensitization after challenge with 1.25 mg/kg of the drug on days 11, 21, and 28. To investigate the role of opioidergic system in the induction and expression of behavioral sensitization, long-acting but non-selective opioid antagonist naltrexone was administrated prior to the daily injections of and challenge with methamphetamine, respectively. Our results show that the expressions of behavioral sensitization were attenuated by pretreatment with 10 or 20 mg/kg of naltrexone either during the induction period or before methamphetamine challenge when they were tested on days 11 and 21. These results indicate that repeated injection with methamphetamine dose-dependently induced behavioral sensitization in mice, and suggest the involvement of opioid receptors in the induction and expression of methamphetamine-induced behavioral sensitization.

show abstract

“…Tolerance to the LH secreto ry effects of naloxone has been demonstrated following a single injection of the antagonist [21]. An increase in the number of opiate binding sites in the brain, resulting from either acute [24,25] or chronic [15,27,30,31] exposure to narcotic antagonists, might account for the observed de cline in effectiveness o f naloxone in enhancing LH secre tion. If these new binding sites are involved in the decline in effectiveness of the naloxone pellet, they are presumably re sponsive to EOP but not morphine.…”

Section: Discussionmentioning

confidence: 99%

Effects of a Sustained-Release Naloxone Pellet on Luteinizing Hormone Secretion in Female Rats

Gabriel¹,

Simpkins²

1983

Neuroendocrinology

View full text Add to dashboard Cite

Studies were undertaken to develop a naloxone implant capable of chronically blocking opioid receptors for several weeks in an effort to evaluate the effect of this prolonged narcotic antagonism on luteinizing hormone (LH) secretion in female rats. Antagonism of opiate receptors was achieved with a tablet formulation which contained 75 mg naloxone free base and a high content of the insoluble binding material, Mg stearate. Subcutaneous placement of this implant prevented morphine-induced analgesia for 2 weeks and antagonized the LH suppressory effects of morphine (15 or 30 mg/kg) administration. Thus, this naloxone delivery system is capable of chronically occupying the opioid receptors which mediate morphine’s effects on analgesia and LH secretion. Despite this, the naloxone pellet only moderately enhanced the initial rate of increase in LH secretion following ovariectomy (day 1) and was ineffective in further augmenting LH secretion at 3 and 7 days after implantation. In rats which were ovariectomized and implanted immediately with estradiol-containing Silastic capsules, the naloxone pellet was ineffective in altering LH secretion 1, 3 or 7 days later. Thus, while chronic exposure to naloxone persistently antagonizes the pharmacologic actions of morphine, the naloxone pellet only transiently blocked the tonic inhibitory effect of endogenous opioid peptides. The mechanism by which the LH secretory effects of naloxone are lost following chronic exposure to the antagonist are at present unknown, but may involve the activation of compensatory mechanisms which are inhibitory to LH secretion.

show abstract

Supersensitivity of brain opiate receptor subtypes after chronic naltrexone treatment

Cited by 87 publications

References 7 publications

Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease

Modification of central dopaminergic mechanisms by continuous levodopa therapy for advanced Parkinson's disease

Attenuation of methamphetamine-induced behavioral sensitization in mice by systemic administration of naltrexone

Effects of a Sustained-Release Naloxone Pellet on Luteinizing Hormone Secretion in Female Rats

Contact Info

Product

Resources

About