PubMed Health⌕ Search

Biomedical subjects

R F Ritzmann

Publications and source records attributed to R F Ritzmann.

At least 37 records · Page 2Linked to original sources
PubMed1985

Neuropeptides differentially effect various forms of morphine tolerance.

Two different forms of tolerance to morphine were shown to develop. One form, environment dependent (ED), was associated with cues paired with the arrival of the drug. The second form of tolerance, environment independent (EI), was not dependent on any cues. ED tolerance was induced using a multiple injection model in which a cue (orange scent) preceeded each morphine injection (ip). After 12 days the animals were tolerant to the i.p. injection. However if morphine was injected i.c.v. tolerance was no longer evident. EI tolerance was induced by a pellet implant method. These animals were tolerant to morphine regardless of the route of administration. Peptides arginine vasopressin (AVP) and cyclo (Leu-Gly) (cLG) were tested for their ability to alter tolerance. AVP was found to facilitate the development of ED tolerance but had no effect on EI tolerance. On the other hand cLG blocked the development of EI tolerance without affecting ED tolerance. The determination of brain morphine levels indicated that the ED tolerance produced by this method is dispositional while EI tolerance is functional.

Animals↗
PubMed1983

Cyclo(Leu-Gly) attenuates the striatal dopaminergic supersensitivity induced by chronic morphine: agonist binding to D2 dopamine receptors correlates with stereotypic behavior.

We have previously shown that MIF and its structural analog, cyclo-(Leu-Gly), block analgesic tolerance and some signs of physical dependence following chronic opiate administration. The mechanism of action of these peptides has not been clearly elucidated. The data presented here suggests that chronic opiate administration causes a behavioral supersensitivity to dopamine (DA) agonists which is highly correlated with an increase in D2-Hi receptor affinity for DA agonists, but not antagonists. Both the behavioral and receptor changes are blocked by prior administration of cyclo(Leu-Gly). This suggests that the ability of cyclo(Leu-Gly) to block the development of opiate addictive states may involve DA synaptic elements.

Animals↗
PubMed1981

Opiate dependence following acute injections of morphine and naloxone: the assessment of various withdrawal signs.

The injection of high dose of naloxone 15 minutes after a single injection of morphine in mice was found to produce a jumping response which was behaviorly similar to the jumping response observed during the withdrawal from chronic morphine administration. In addition the jumping response following the acute administration of morphine-naloxone was increased by the injection of atropine and attenuated by oxotremorine. These data are consistent with the reports of effect of these cholinergic drugs on the jumping response which occurred during withdrawal after chronic morphine administration. However, other symptoms associated with opiate withdrawal (hypothermia, weight loss and diarrhea) were not produced by the acute injection of morphine-naloxone. It is therefore suggested that this single injection paradigm is particular to the jumping response rather than a demonstration of the rapid development of opiate dependence.

Animals↗
PubMed1980

Strain differences in the development of acute tolerance to ethanol.

C57B1/6 mouse brain serotonin levels were depleted by feeding animals a diet containing no tryptophan. When such mice were injected with ethanol, they were found to lose their righting reflex for significantly longer periods and to have a lower body temperature than control animals. Animals consuming the diet containing no tryptophan metabolized ethanol more slowly than controls. Although daily injections of kynurenine reinstated ethanol metabolism to normal, the duration of loss of righting reflex and the hypothermia induced by ethanol were unaffected by kynurenine pretreatment. Tryptophan (75 mg/kg) administered six hours prior to ethanol injection returned brain serotonin levels to normal in tryptophan-deprived mice. Mice injected with tryptophan were found to respond to ethanol as did the control animals. When brain ethanol levels were determined at the time the animals lost their righting reflex and when animals regained their righting reflex, tryptophan-deprived mice were found to regain the righting reflex at the same brain ethanol levels as those at which such animals lost their righting reflex. Tryptophan administration to tryptophan-deprived mice resulted in their regaining the righting reflex at higher ethanol levels than those at which they lost the reflex. Similar experiments were carried out on C3H/HeJ and DBA/J2 mice. The results indicate that C3H mice developed some acute tolerance while DBA mice failed to develop any acute tolerance. The possibility exists that the strain difference in the degree of sensitivity to ethanol observed in these mice may be due to differing abilities to develop acute tolerance.

Animals↗
PubMed1980

Inhibition of neuroleptic-induced dopamine receptor supersensitivity by cyclo (Leu-Gly).

Behavioral supersensitivity of dopamine receptors was induced in mice by chronic administration of haloperidol (1 mg/kg/day for 21 days) and its subsequent withdrawal for 48 hr. This was evidenced by enhanced spontaneous locomotor activity and hypothermic responses to a dopamine agonist, apomorphine. Concurrent administration of cyclo (Leu-Gly), the enzymatically resistant diketopiperazine, an analog of melantropin release inhibiting factor, blocked haloperidol-induced dopamine receptor supersensitivity as evidenced by the blockade of apomorphine induced responses. Since many studies have linked the development of neuroleptic induced tardive dyskinesias with enhanced sensitivity of brain dopamine receptors, and the latter was blocker by cyclo (Leu-Gly), this agent may be of value in preventing the development of symptoms of neuroleptic-induced tardive dyskinesias.

Animals↗
PubMed1980

An inhibitor of opioid peptide degradation produces analgesia in mice.

Bacitracin, a known inhibitor of brain peptidases which degrade the enkephalins and endorphins, produced dose-dependent analgesia in mice when injected into the lateral ventricle of the brain as determined by the tail-flick assay. The analgesic response peaked at 15 min post-injection but was reduced to control levels by 3.5 hours. Naloxone reversed the analgesic response to bacitracin, suggesting that opiate receptors may be involved. It is proposed that bacitracin produces analgesia by preventing the enzymatic destruction of endogenously released opioid peptides.

Analgesics↗
PubMed1980

Development of narcotic tolerance and physical dependence: effects of Pro-Leu-Gly-NH2 and cyclo (Leu-Gly).

Administration of Pro-Leu-Gly-NH2 (MIF) and cyclo (Leu-Gly) blocked the development of tolerance to and physical dependence on morphine, induced by the pellet implanation procedure in mice. Inhibition of tolerance development by peptides was evidenced by the presence of an analgesic response (increase in jump threshold) as determined by measuring the jump threshold to an increasing electric current, after a challenge dose of morphine (40 mg/kg). The same dose of morphine did not alter the jump threshold in morphine tolerant mice which were injected with saline prior to pellet implantation. The inhibition of the development of physical dependence on morphine by these peptides was evidenced by the antagonism of the hypothermic response which occurs during abrupt or naloxone-induced withdrawal. The naloxone-induced withdrawal jumping response was unaffected by these peptides. Dose-response experiments indicated that cyclo (leu-Gly) was much more potent than MIF in these tests. These peptides, when given after the development of tolerance and dependence, did not modify either the analgesic response to morphine or the symptoms of abrupt and naloxone-precipitated withdrawal. The inhibition of development of analgesic tolerance and physical dependence was not associated with changes in brain morphine concentration. The data indicate that these peptides do not interfere withe the morphine-morphine receptor complex formation but alter a subsequent step in the genesis of some aspects of tolerance and dependence processes.

Analgesia↗
PubMed1980

Neurohypophyseal peptide influences on ethanol tolerance and acute effects of ethanol.

The neurohypophyseal hormone, arginine vasopressin (AVP), was previously shown to prolong the duration of ethanol tolerance in mice. Since drug tolerance and certain memory-related processes are examples of CNS adaptation, these phenomena have been proposed to share underlying mechanisms. We investigated the effects on ethanol tolerance of two other neurohypophyseal peptides, both of which modulate memory consolidation or retrieval of information. (Des-9-glycinamide, 8-lysine) vasopressin (DGLVP), like AVP, maintained ethanol tolerance in C57Bl mice, while cyclo(Leu-Gly) (cLG), at an equimolar dose, was ineffective. Thus, various neurohypophyseal peptides may differentially influence CNS adaptive phenomena. Direct peptide effects on ethanol-induced hypothermia and "sleep time," the parameters used to evaluate ethanol tolerance, were also determined. AVP per se caused hypothermia in mice, but neither AVP nor cLG affected ethanol-induced hypothermia. Both peptides, however, increased "sleep time" after acute ethanol administration. Although these direct peptide-ethanol interactions do not account for the observed peptide effects on tolerance, the findings emphasize the importance of using several parameters to assess ethanol tolerance.

Animals↗
PubMed1980

Characterization of acute and chronic tolerance in mice selected for inherent differences in sensitivity to ethanol.

Long sleep (LS) and short sleep (SS) mice have been selectively bred for differences in response to hypnotic doses of ethanol. In these studies, SS mice were found to develop functional tolerance faster than LS mice during a regimen of multiple injections of ethanol. No evidence for the development of acute tolerance was evident in mice of either of the selected lines or the offspring of an LS by SS cross (F1), and no metabolic tolerance developed during the 5-day alcohol treatment period.

Animals↗
PubMed1979

The effect of selective lesions of brain noradrenergic systems on the development of barbiturate tolerance in rats.

A method for chronic infusion of barbiturates into the central nervous system of rats was developed and used to study the importance of noradrenergic systems in the development of barbiturate tolerance. Destruction of noradrenergic neurons by intraventricular administration of 6-hydroxydopamine or by specific lesions of the dorsal or ventral noradrenergic bundles prevented the development of barbiturate tolerance without altering the animal's response to the acute administration of barbiturate.

Animals↗
PubMed1979

Prolyl-leucyl-glycinamide, cyclo(leucylglycine), and derivatives block development of physical dependence on morphine in mice.

Pro-Leu-Gly-NH2 (MIF) and several structural analogues, all injected in 50-microgram doses daily in mice receiving morphine chronically, were found to prevent development of physical dependence as measured by changes in body temperature associated with naloxone-induced withdrawal. Dose-response studies, using again a protocol of daily injections of peptide at 50, 5, 0.5, 0.05, 0.005 microgram per mouse revealed MIF and cyclo(Leu-Gly) to be the most potent peptides and to be effective in blocking physical dependence to morphine at a dose as low as 0.5 and 0.05 microgram per mouse, respectively. The benzyloxycarbonyl derivative of MIF, Pro-Leu, and Pro- -Leu exhibited significant activities down to a dose of 5 microgram of peptide per mouse.

Animals↗
PubMed1979

Blockage of narcotic-induced dopamine receptor supersensitivity by cyclo(Leu-Gly).

We have previously reported that the administration of cyclo(Leu-Gly) to mice prior to morphinization blocked the development of tolerance to the analgesic effects of morphine as well as the development of some signs of physical dependence. In the present series of experiments, the effect of the same peptide treatment on changes in dopamine receptor sensitivity induced by chronic morphine treatment were determined. Changes in dopamine receptor sensitivity were determined by measuring (i) the effect of the dopamine agonist apomorphine on locomotor activity and (ii) the hypothermic response to another dopamine agonist, piribedil. Mice that had received the chronic morphine treatment were found to require significantly less apomorphine to produce an increase in locomotor activity, and they exhibited a significantly greater hypothermic response to piribedil than did morphine-naive mice. The injection of 0.2 mumol of cyclo(Leu-Gly) per mouse 2 hr prio to morphine treatment prevented this increased response to both dopamine agonists. Administration of the peptide after the tolerance and dependence had developed did not alter morphine tolerant and dependent states states or the enhanced response to apomorphine or piribedil. It is concluded that dopamine receptor supersensitivity may be involved in the development of narcotic tolerance and physical dependence.

Animals↗