Biomedical subjects

M R Zarrindast

Publications and source records attributed to M R Zarrindast.

At least 37 records · Page 2Linked to original sources

PubMed2000

Effects of adrenoceptor agents on apomorphine-induced licking behavior in rats.

In the present study, intraperitoneal (IP) administration of the dopaminergic receptor agonist apomorphine (0.1, 0.25, and 0.5 mg/kg) induced a dose-dependent licking in rats. The intraperitoneal injection of the alpha1'''adrenoceptor agonist phenylephrine (1-8 mg/kg) but not the alpha2-adrenoceptor agonist clonidine (0.025-0.05 mg/kg) decreased licking induced by apomorphine. The alpha-adrenoceptor antagonists prazosin, phenoxybenzamine, and yohimbine also reduced the apomorphine response significantly. The response induced by phenylephrine was decreased by a dose of prazosin. The beta1-adrenenocepor agonist dobutamine and beta2-adrenenocepor agonist salbutamol did not alter the apomorphine response. However, beta2-adrenenocepor antagonists atenolol and propranolol reduced the apomorphine effect. It may be concluded that alpha1- and possibly beta1-adrenoceptor mechanisms may be involved in modulation of licking behavior.

Adrenergic Agents↗

PubMed2000

Effect of nicotine on sniffing induced by dopaminergic receptor stimulation.

Effects of nicotine on sniffing induced by amphetamine and apomorphine have been tested in rats. Intraperitoneal (i.p.) administration of nicotine (0.5 and 1 mg/kg), amphetamine (1-6 mg/kg) or apomorphine (0.1-1 mg/kg) induced sniffing. Nicotine (0. 25-1 mg/kg) potentiates sniffing induced by amphetamine (1 mg/kg). Nicotine (1 mg/kg) also potentiates the response induced by different doses (0.1-1 mg/kg) of apomorphine. Atropine induced sniffing and increased the response of both amphetamine and nicotine. Higher doses of hexamethonium decreased the sniffing response induced by amphetamine and the response induced by combination of amphetamine and nicotine. Sulpiride reduced the response induced by nicotine or amphetamine plus nicotine, while SCH23390 reduced normal sniffing behaviour of the animals and sniffing induced by either amphetamine or amphetamine plus nicotine. The data may indicate that nicotinic receptor mechanism(s) may be involved in the sniffing induced by dopaminergic receptor stimulation.

Amphetamine↗

PubMed2000

Role of cholecystokinin receptors in induction of antinociception in hot-plate test.

In the present study, the antinociceptive effect of cholecystokinin receptor agonists in the hot-plate test in mice has been evaluated. Subcutaneous administration of cholecystokinin octapeptide (cholecystokinin-8; 0.001, 0.005, 0.01, 0.05, and 0.1 mg/kg), unsulfated cholecystokinin octapeptide (cholecystokinin-8U; 0.1 mg/kg) or caerulein (0.25 mg/kg) produced antinociception. Administration of the cholecystokinin tetrapeptide (cholecystokinin-4; 0.25, 0.5 and 1.0 mg/kg) had no effect in the hot-plate test. Subcutaneous injection of the selective cholecystokinin receptor antagonists, MK-329 (0.125, 0.25 and 0.5 mg/kg) or L-365,260 (0.125, 0.25 and 0.5 mg/kg), produced no antinociceptive response. When the animals were pretreated with the cholecystokinin receptor antagonists or naloxone (0.5 and 1 mg/kg), a significant decrease in the antinociceptive response induced by cholecystokinin-8 and caerulein was obtained. The results indicate that single administration of cholecystokinin receptor agonists could produce an antinociceptive effect which is probably mediated via cholecystokinin receptors. With respect to the results obtained from morphine and naloxone administration, it is concluded that there may be an interaction between cholecystokinin and opiate mechanisms.

Analgesia↗

PubMed2000

Antinociceptive effect of intracerebroventricular administration of cholecystokinin antagonist in nerve-ligated mice.

In the present study we investigated the effects of intracerebroventricular injection of caerulein, the cholecystoki nin receptor agonist and proglumide, the receptor antagonist on morphine response in the sciatic nerve ligation in mice. Subcutaneous administration of morphine induced antinociception in the both intact and ligated mice, however, the response of the opioid was lower in the ligated mice as compared with the intact animals. Caerulein induced antinociception in the non-ligated but not in the nerve-ligated animals. Combination of caerulein with morphine elicited higher response in ligated animals, however, the response induced in ligated animals was much more prominent. Proglumide alone did not elicit any response in both animal groups. The antagonist decreased the response of caerulein in the nonligated mice. Low doses of proglumide in the combination with caerulein induced antinociception in the ligated mice. We conclude that cholecystokinin receptor mechanism(s) may alter morphine resistance induced by nerve ligation.

Analgesics, Opioid↗

PubMed2000

Effect of imipramine on tolerance to morphine antinociception in the formalin test.

In this study, the effect of imipramine on morphine antinociception in tolerant and non-tolerant mice in the formalin test, was investigated. Subcutaneous administration of different test doses of morphine (3, 6 and 9 mg/kg) and intraperitoneal injection of test doses of imipramine (10, 20 and 40 mg/kg) induced a dose-dependent antinociception in non-tolerant mice, both in the first and second phases of the formalin test. The combination of morphine (1 mg/kg) with imipramine (10 mg/kg) showed a potentiated response in the second phase of the test. Combination of a single dose of morphine (1.5 mg/kg) with lower doses of imipramine (2, 4 and 8 mg/kg) did not show potentiation. The antinociceptive response of either morphine or morphine plus imipramine was reduced by the opioid receptor antagonist naloxone (2 mg/ kg). In order to induce tolerance, mice were treated subcutaneously with morphine (50 mg/kg) once daily for 3 days. On day 4, the antinociceptive effect of test doses of morphine or imipramine were assessed. Tolerance to the responses of test doses of morphine (3, 6 and 9 mg/kg), but not imipramine (10, 20 and 40 mg/kg) in both phases of the test was observed. Administration of lower dose of imipramine (4 mg/kg) before the test doses of morphine (3, 6 and 9 mg/kg) was not able to alter the expression of morphine tolerance. When imipramine was used during development of tolerance, either on days 1 and 2 or on days 2 and 3, the morphine tolerance in the second phase of the test was reduced. It is concluded that opioid receptor mechanism(s) may mediate the antidepressant-induced antinociception, however, imipramine may be useful in inhibiting morphine tolerance.

Analgesics, Opioid↗

PubMed1999

Adenosine A(2) receptors inhibit morphine self-administration in rats.

In the present study, the effect of adenosine receptor agonists and antagonists on morphine self-administration was investigated. Intravenous administration of morphine (0.3-3 mg/kg/injection) induced dose-dependent self-administration. The adenosine receptor antagonists, theophylline (2.5, 5, 10 mg/kg) and 3, 7-Dimethyl-1-propargylxanthine (DMPX; 0.25, 0.5, 1 mg/kg), when injected 1 h before the start of the test, reduced the number of self-administered morphine infusions. The adenosine receptor antagonists when administered in the training period (11 days) greatly increased the number of morphine infusions, however, they did not induce any response by themselves. 5'-N-ethylcarboxamido-adenosine (NECA; 0.5, 1 mg/kg) and 4-[2-[[6-Amino-9-(N-ethyl-beta-D-ribofuranuronamidosyl)-9H-purin-2 -yl ]amino] ethyl]benzenepropanoic acid (CGS21680; 0.001, 0.01, 0.025, 0. 05 mg/kg), given 1 h before the start of the test, increased morphine self-administration. Although the adenosine agonists, when injected during training period (11 days), reduced morphine self-administration. Furthermore, NECA, but not CGS21680, induced significant self-administration. The adenosine A(1) receptor agonist, N(6)-cyclohexyladenosine (CHA; 0.01, 0.1, 0.25, 0.5 and 1 mg/kg), and the adenosine A(1) receptor antagonist, 8-phenyletheophylline (2, 4, 6, 8 mg/kg), themselves neither altered morphine infusion nor induced any response. These results indicate a role for adenosine A(2) receptors in the expression and/or development of morphine self-administration.

Animals↗

PubMed1999

Effects of GABAergic system on naloxone-induced jumping in morphine-dependent mice.

The effect of GABA (gamma-aminobutyric acid system) receptor agonists and antagonists on naloxone-induced jumping in morphine-dependent mice was examined. Intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) injection of different doses of the GABA(B) receptor agonist, baclofen (2.5, 5 and 10 mg/kg), reduced naloxone-induced jumping in morphine-dependent mice. The i.p. administration of the GABA(B) receptor antagonist, CGP35348 (P-[3-aminopropyl]-p-diethoxymethyl-phosphinic acid), but not the i.c.v. injection of the drug, increased naloxone-induced jumping. The antagonist also decreased the baclofen response. Administration of the GABA(A) receptor agonist, muscimol, but not the GABA(A) receptor antagonists bicuculline and picrotoxin, decreased the naloxone response in morphine-dependent animals. It is concluded that both GABA(A) and GABA(B) receptor subtypes may have an inhibitory influence on naloxone-induced withdrawal jumping in mice.

Animals↗

PubMed1999

Effects of adenosine receptor agents on the expression of morphine withdrawal in mice.

Effects of different doses of adenosine receptor agonists and antagonists on naloxone-induced jumping and diarrhea in morphine-dependent mice were studied. The adenosine A1 receptor agonists, N6-cyclohexyladenosine (CHA: 0.1, 0.25 and 0.5 mg kg(-1)) and R-isomer of N6-phenylisopropyladenosine (R-PIA: 0.1, 0.3 and 1 mg kg(-1)), decreased jumping and diarrhea induced by naloxone in morphine-dependent mice. The adenosine A1 receptor antagonist, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX: 0.3-9 mg kg(-1)), increased jumping but decreased diarrhea. The adenosine A2 receptor agonist, 5'-(N-cyclopropyl)-carboxamidoadenosine (CPCA), decreased jumping and diarrhea. However, the adenosine A2 receptor antagonist, 3,7-dimethyl-1-propargylxanthine (DMPX: 0.5 and 1 mg kg(-1)), did not elicit any response in this respect. DPCPX (0.3 and 3 mg kg(-1)), decreased the inhibition of jumping and diarrhea induced by CHA (0.5 mg kg(-1)), while DMPX (0.5 and 1 mg kg(-1)), decreased the inhibition of diarrhea induced by CPCA (0.1 mg kg(-1)). It is concluded that jumping induced by naloxone in morphine-dependent mice may be modified by the adenosine A receptor mechanism(s) and diarrhea induced by the opioid receptor antagonist could be mediated by the adenosine A1 and A2 receptors.

Adenosine↗

PubMed1999

Baclofen and antidepressant--induced antinociception in formalin test: possible GABA(B) mechanism involvement.

In this study, the influences of GABA(B) agents on antidepressant-induced antinociception in the mouse formalin test have been investigated. The GABA(B) receptor agonist baclofen (2.5, 5 and 10 mg/kg) induced a dose-dependent antinociception in the second phase of the formalin test. This response was inhibited by the GABA(B) receptor antagonist, CGP35348 [P-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid], in a dose-dependent manner. The antagonist by itself also induced antinociception. Single administration of the antidepressants citalopram (10, 20, 40 and 80 mg/kg), desipramine (20, 40, 80 mg/kg) or imipramine (10, 20 and 40 mg/kg) also induced antinociception in both phases of the formalin test. CGP35348 (100 and 200 mg/kg) pretreatment reduced the response induced by the tricyclic antidepressants. A combination of baclofen with the tricyclic antidepressant did not potentiate antinociception induced by antidepressants, but a decrease in the response induced by higher dose of baclofen was shown. It is concluded that GABA mechanism(s) may modulate the antidepressant-induced antinociception.

Analgesics, Non-Narcotic↗

PubMed1999

Influence of different adrenoceptor agonists and antagonists on physostigmine-induced yawning in rats.

In the present study, effects of adrenoceptor agonists and antagonists on physostigmine-induced yawning was investigated. Intraperitoneal (i.p.) injection of different doses of physostigmine (0.03, 0.05, 0.1, and 0.2 mg/kg) induced yawning in rats. The maximum response was obtained by 0.2 mg/kg of the drug. The alpha1-adrenoceptor agonist, phenylephrine, and the alpha2-adrenoceptor agonist, clonidine, decreased yawning induced by physostigmine. Prazosin and higher doses of phenoxybenzamine reduced the inhibitory effect of phenylephrine. Higher doses of yohimbine also reduced the clonidine response. The adrenoceptor antagonists, prazosin, phenoxybenzamine, and propranolol, did not significantly alter the physostigmine response. However, yohimbine, or lower doses of prazosin, decreased the physostigmine response. It may be concluded that alpha1- and alpha2-adrenoceptor stimulation decreases the physostigmine-induced yawning behavior in rats.

Adrenergic Agonists↗

PubMed1999

Effects of dopaminergic agents on antinociception in formalin test.

Morphine caused a dose-related antinociception in early phase and late phase of formalin test in mice. The D2 dopamine agonist quinpirole, but not the D1 dopamine agonist SKF 38393, increased the antinociceptive effect of morphine in both phases of the test. The antinociceptive effect of quinpirole also was decreased by sulpiride or domperidone pretreatment in the early phase of test. The D1 antagonist SCH23390, the D2 antagonist sulpiride, or the peripheral D2 dopamine antagonist domperidone, increased the morphine effect. Single administration of SKF38393, quinpirole, SCH23390, sulpiride, and domperidone also induce antinociception. The response of SCH23390, but not that of other dopamine agents, was antagonized with naloxone. The effects of the drugs alone and in combination with morphine have been discussed.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

PubMed1999

Effects of CCK antagonists on GABA mechanism-induced antinociception in the formalin test.

In this work, the influences of CCK receptor antagonists on antinociception induced by the GABA receptor agonist, baclofen, and the GABA uptake inhibitor, THPO, in the formalin test have been studied. GABA-B agonist baclofen (0.75, 1.25 and 2.5 mg/kg), THPO, a GABA uptake inhibitor (1 and 2 mg/kg) and morphine (1.5, 3 and 6 mg/kg) induced antinociception in both phases of the formalin test in mice. The selective CCK receptor antagonists, L-365,260, MK-329 (0.05, 0.125 and 0.25 mg/kg) and non-selective CCK receptor antagonist, proglumide (2.5, 5, 10 and 20 mg/kg) induced antinociception only in high doses. The CCK receptor antagonists potentiated baclofen (0.75, 1.25 and 2.5 mg/kg) or THPO (1 and 2 mg/kg) responses. It may be concluded that the CCK receptor mechanism may interact with GABA-function in its antinociceptive effect.

Analgesics, Non-Narcotic↗

PubMed1999

Effect of nicotine on apomorphine-induced licking behaviour in rats.

In the present study, the dopaminergic receptor agonist apomorphine (0.1, 0.25 and 0.5 mg/kg) induced a dose-dependent licking in rats. Nicotine administration (0.025-250 microg/kg) altered the apomorphine-induced licking. The lower doses of nicotine (0.05 and 0.5 microg/kg) increased while the higher dose of the drug (250 microg/kg) reduced the apomorphine response. The antimuscarinic drug atropine (2.5 and 5 mg/kg) reduced the effects of apomorphine or nicotine plus apomorphine. The central nicotinic receptor antagonist mecamylamine (0.05, 0.25 and 0.5 mg/kg) also reduced the response induced by apomorphine or nicotine plus apomorphine. However, the peripheral nicotinic receptor antagonist hexamethonium (2.5, 5 and 10 mg/kg) reduced the response induced by nicotine plus apomorphine but not that elicited by apomorphine alone. The results indicate that the nicotinic receptor mechanism(s) may interact with apomorphine-induced licking in rats. Although central nicotinic and cholinergic mechanisms may be involved in the licking induced by apomorphine, peripheral nicotinic mechanism may be involved in the nicotine-induced increased apomorphine effect.

Animals↗

PubMed1999

Cholecystokinin and morphine-induced hypothermia.

The effects of cholecystokinin-8 sulfate (CCK-8), cholecystokinin-8 unsulfate (CCK-8U), cholecystokinin-4 (CCK-4), caerulein and morphine on mice core body temperature have been studied in the present work. Subcutaneous injection of different doses of caerulein (0.05, 0.1 and 0.5 mg/kg), CCK-8 (0.05, 0.1 and 0.25 mg/kg) and morphine (10, 20 and 30 mg/kg) induced hypothermia. CCK-8U and CCK-4 did not elicit any response. The hypothermic response induced by caerulein, a CCK-related decapeptide but not morphine was decreased by selective CCK(A) receptor antagonist MK-329. However, the hypothermia induced by morphine but not caerulein was reduced by opioid antagonist naloxone. When morphine plus caerulein was administered a higher hypothermia was induced. Pretreatment of animals with L-365 260, a selective CCK(B) receptor antagonist did not alter the hypothermia induced by the drugs. The response induced by combination of the both drugs was decreased by MK-329. Administration of CCK antagonists MK-329 and L-365 260 to mice did not exert any effect on temperature. It is concluded that the CCK(A) receptor mechanism may be involved in the hypothermic effect of CCK agonists or morphine, while opioid receptor mechanism is not involved in CCK receptor agonists' response.

Animals↗

PubMed1999

The development of cross-tolerance between morphine and nicotine in mice.

In the present study, cross-tolerance between nicotine and morphine in mice has been investigated. Mice were treated subcutaneously with three doses of morphine (12.5, 25 and 50 mg/kg) once daily, for 3 days in order to produce tolerance to morphine and nicotine antinociception. Tolerance only developed in the high dose group. On the 4th day, the antinociceptive effect of three test doses of morphine (3, 6 and 9 mg/kg) or nicotine (0.01, 0.05 and 0.1 mg/kg) were assessed. Tolerance to the responses of both drugs were observed. Intraperitoneal administration of nicotine (2 mg/kg) three times a day for a period of 12 days, also induced tolerance to the antinociceptive effects of both morphine and nicotine. When animals were tested on the 13th day, the antinociceptive responses of morphine or nicotine were reduced. Another group of animals was treated with low doses of morphine daily (12.5 or 25 mg/kg) plus nicotine (2 mg/kg) three times daily for 3 days. In this group of animals, the antinociception to either morphine or nicotine was tested. Combination of both drugs caused an increase in tolerance to either drug. It is concluded that there is cross-tolerance between the two drugs.

Analgesics↗

PubMed1999

Synthesis, conformational analysis and antinociceptive activity of 1-[N-methyl-(2-phenylethyl)amino]methyl-1,2,3,4-tetrahydroisoquinoline derivatives.

New derivatives of 1-[N-methyl-(2-phenylethyl)amino]methyl-1,2,3,4-tetrahydroisoquinoline were synthesized. The antinociceptive activity of the compounds, determined by the mouse tail-flick test, showed that the introduction of a hydroxy substituent in position 5 of the isoquinoline nucleus generated compounds 4c and 5c, which were as potent as codeine. Conformational analysis and superimposition of energy minima conformers of the compounds on phenazocine revealed that the main proposed opioid pharmacophores were well matched.

Analgesics↗

PubMed1999

Baclofen-induced antinociception and nicotinic receptor mechanism(s).

In this study, the influences of nicotinic receptor agents on baclofen-induced antinociception in the tail-flick test have been studied. Intraperitoneal administration of baclofen (2.5, 5 and 10 mg/kg) to mice induced a dose-dependent antinociception in the tail-flick test. Subcutaneous injection of nicotine (0.5-2.5 mg/kg) also caused a dose-dependent antinociceptive response. Intracerebral (10 and 20 microg/mouse) but not intraperitoneal administration of hexamethonium (5 and 10 mg/kg) to mice decreased the response of both nicotine and baclofen. However, administration of the GABA(B) antagonist CGP 35348 (100 and 200 mg/kg) decreased the response induced by baclofen but not by nicotine. It is concluded that at least part of the baclofen-induced antinociception may be mediated through a nicotinic mechanism.

Analgesics↗

PubMed1999

Cholecystokinin receptor mechanism(s) and morphine tolerance in mice.

In a previous work, the effects of cholecystokinin receptor agonists on tolerance to morphine antinociception were evaluated. In the present study, the influence of cholecystokinin antagonists on the inhibition of tolerance to morphine antinociception by cholecystokinin agonists has been investigated. Maximum tolerance to morphine antinociception was obtained by morphine administration (50 mg/kg) to mice once daily for 4 days. The cholecystokinin receptor agonists caerulein (0.005 mg/kg) or cholecystokinin-8 (0.01 mg/kg) but not unsulfated cholecystokinin-8 (0.01 mg/kg) decreased the development of tolerance to morphine (9 mg/kg). The cholecystokininA receptor antagonist MK-329 (1 mg/kg) or the cholecystokininB receptor antagonist L-365,260 (0.25, 0.5 and 1 mg/kg) also diminished the tolerance to morphine antinociception. When animals were challenged with different doses of MK-329 (0.25, 0.5 and 1 mg/kg) against cholecystokinin-8 (0.01 mg/kg), caerulein (0.005 mg/kg) or unsulfated cholecystokinin-8 (0.01 mg/kg) on day 4 in tolerant mice, different response were obtained. Higher doses of MK-329 (1 mg/kg) caused a small decrease in attenuation of the morphine tolerance induced by cholecystokinin-8 and caerulein. Low doses of L-365, 260 diminished the effect of cholecystokinin-8 on morphine tolerance. Conversely high doses of the drug potentiated the response of caerulein (0.005 mg/kg). When animals were treated with MK-329 or L-365,260 before unsulfated cholecystokinin-8, reduction of the tolerance to morphine antinociception was obtained. These data indicate that both cholecystokinin receptors may modulate morphine tolerance.

Animals↗