L. Sorrentino

The interaction of peripherally and centrally administered dexamethasone and RU 38486 on morphine analgesia in mice

1. Dexamethasone or RU 38486 were administered intraperitoneally or intracerebroventricularly to mice 10 or 120 min before morphine administration. The interaction of these drugs with the analgesic effects of morphine was examined using the hot plate test. 2. Dexamethasone i.p. pretreatment reduced analgesic responses to morphine injected 120 min but not 10 min after dexamethasone; i.c.v. injection of dexamethasone 10 and 120 min before morphine administration was effective in reducing morphine analgesia. 3. RU 38486 i.c.v. pretreatment (but not i.p. pretreatment) performed 120 (but not 10) min before morphine administration enhanced morphine analgesic effects. 4. These results, particularly the effects of drug interaction for i.c.v. administration, strongly confirm a central site for dexamethasone and RU 38486 action.

Dexamethasone-induced selective inhibition of the central μ opioid receptor: functional in vivo and in vitro evidence in rodents

1 Endogenous corticosteroids and opioids are involved in many functions of the organism, including analgesia, cerebral excitability, stress and others. Therefore, we considered it important to gain information on the functional interaction between corticosteroids and specific opioid receptor subpopulations. 2 We have found that systemic administration (i.p.) of the potent synthetic corticosteroid, dexamethasone, reduced the antinociception induced by the highly selective μ agonist, DAMGO or by less selective μ agonists morphine and β‐endorphin administered i.e.v., On the contrary dexamethasone exerted little or no influence on the antinociception induced by a δ1 agonist, DPDPE and a δ2 agonist deltorphin II. Dexamethasone potentiated the antinociception induced by the k agonist, U50,488. 3 In experiments performed in an in vitro model of cerebral excitability in the rat hippocampal slice, dexamethasone strongly prevented both the increase of the duration of the field potential recorded in CA1, and the appearance and number of additional population spikes induced by μ receptor agonists. 4 In both models pretreatment with cycloheximide, a protein synthesis inhibitor, prevented the antagonism by dexamethasone of responses to the μ opioid agonists. 5 Our data indicate that in the rodent brain there is an important functional interaction between the corticosteroid and the opioid systems at least at the μ receptor level, while δ and k receptors are modulated in different ways.

Effects induced by cysteamine on chemically-induced nociception in mice

The effects were investigated of cysteamine--a well known somatostatin depletor--on the pain induced by chemical stimuli in mice. Cysteamine injected intraperitoneally 4 h before the test at doses of 50 and 100 mg/kg reduced the second phase of the licking response which was induced by formalin injected into the hind paw. Furthermore, cysteamine administered at the doses of 10, 50 and 100 mg/kg reduced the writhing induced by acetic acid. Naloxone, yohimbine and CGP 35348 administered in cysteamine-pretreated animals were not able to change the cysteamine antinociceptive effects in the formalin test. Intrathecally injected somatostatin was able to revert the cysteamine antinociceptive effects in the second phase of the formalin test and in the writhing test, whereas intracerebroventricularly injected somatostatin reduced the antinociceptive effects induced by cysteamine in the second phase of the formalin test. Intrathecally injected cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl])--a reported somatostatin antagonist--increased cysteamine antinociceptive effects in the second phase of the formalin test and in the writhing test. These results suggest that somatostatin is involved in the effects of cysteamine on the nociceptive threshold.

Dexamethasone pretreatment reduces the psychomotor stimulant effects induced by cocaine and amphetamine in mice

1. The present study examined a comparison of the effect of DEX on psychomotor stimulant effects of cocaine and amphetamine in mice by using the locomotor activity test. 2. Cocaine (10 mg/kg/i.p.) and amphetamine (5 mg/kg/i.p.) increased markedly locomotor activity of mice whereas DEX per se (0.1-1.0-10 mg/kg/i.p.) did not modify the activity of control mice. 3. DEX pretreatment decreased the stimulating effects induced both by cocaine and amphetamine but no consistent dose-related effects were observed. 4. The results suggest that DEX may play an important role on the stimulating effects of cocaine and amphetamine and that it may be of some utility in the clinical management of psychostimulants abuse.

Actinomycin D blocks the reducing effect of dexamethasone on amphetamine and cocaine hypermotility in mice.

1. The present study examined a time-course effect of dexamethasone (DEX) on amphetamine and cocaine-induced hypermotility in mice and the influence of actinomycin D (dactinomycin), a protein synthesis inhibitor, on DEX effects. 2. Amphetamine (5 mg/kg IP) and cocaine (10 mg/kg IP) increased markedly the locomotor activity of mice, whereas DEX alone (0.1-1.0-10 mg/kg IP) did not modify the activity of control mice. 3. DEX pretreatment 0, 15, 30, 60 and 120 min before amphetamine or cocaine strongly decreased both amphetamine and cocaine effects, but no dose-related effect was observed. 4. The time-course study performed with DEX revealed differences in its reducing effect on cocaine and amphetamine hypermotility when the groups of animals treated with the steroid immediately before the cocaine (or amphetamine) injection were compared to those treated with the steroid later (15, 30, 60 and 120 min). 5. Furthermore, actinomycin D was able to block the reducing effect of DEX on both amphetamine and cocaine hypermotility. 6. Therefore, considering that the administration time of the steroid seems to be an important factor for reducing both cocaine and amphetamine hypermotility, and actinomycin D was able to block the reducing effect of the steroid, our study suggests that DEX exerts its reducing effect through a genomic activation.

Effect of des-tyrosine-γ-endorphin on neocortical spike-and-wave spindling in DBA/2J mice

Abstract The effect of a β-endorphin cleavage product devoid of opioid effects, des-tyrosine-γ-endorphin (DTγE) on the neocortical spike-and-wave spindling episodes in the electrocorticogram (ECoG) of DBA/2J mice was studied. DTγE (0.01–1.0 mg/kg, i.p.) dose dependently reduced the spike-and-wave bursts duration. However, the low dose did not induce consistent modifications of the spike-and-wave bursts number while the dose of 0.1 and 1.0 mg/kg induced a progressive diminution. Furthermore, at all doses DTγE did not induce any alterations of the spike-and-wave bursts amplitude, frequency, and desynchronized activity when compared to the pre-drug period. These results indicate that this β-endorphin fragment may affect brain excitability.

Time- and dose-related influence of dexamethasone on morphine-induced hypermotility in mice

The effect of interaction between dexamethasone (DEX) and morphine on locomotor activity in mice was investigated. DEX alone (1.0 and 10 mg/kg i.p.) did not affect the locomotor activity of mice when injected immediately before the beginning of the session. DEX (1.0 mg) injected two hours before the session did not modify the activity of mice whereas the higher dose (10 mg) increased it. Morphine alone (30 mg/kg i.p.) induced a consistent increase in the locomotor activity. DEX (1.0 mg) injected at the same time as morphine reduced the morphine hypermotility, whereas that injected two hours before morphine had no influence on morphine hypermotility. DEX (10 mg) consistently potentiated the morphine hypermotility both when administered together and two hours before morphine. We conclude that DEX exerts an important time-and dose-related influence on morphine-induced hyperactivity in mice.

Phencyclidine reduces inherited neocortical spindling in DBA/2J mice

The role of phencyclidine (PCP) in the control of the spike-and-wave spindling episodes (S&W) which can be spontaneously recorded in the electrocorticogram (ECoG) of DBA/2J mice was investigated. PCP (0.1-0.5-1.0-5.0 mg/kg/i.p.) dose dependently reduced both S&W number and duration of DBA/2J mice. PCP reduction is significant 30-60 min after drug administration and lasts for the whole duration of the recording period (240 min). These results suggest that PCP may play an important regulatory role on brain excitability.

Dexamethasone Reduces the Behavioural Effects Induced by Baclofen in Mice

The present study examines the influence of dexamethasone on the behavioural effects induced by baclofen in mice. The behaviour elements considered were locomotor activity, motor co‐ordination, catalepsy, stereotyped behaviour and antinociception.