Biomedical subjects

M R Zarrindast

Publications and source records attributed to M R Zarrindast.

At least 73 records · Page 4Linked to original sources

PubMed1996

Nicotine attenuates naloxone-induced jumping behaviour in morphine-dependent mice.

In the present study the effect of nicotine on naloxone-induced jumping behaviour in morphine-dependent mice was examined. In addition, the modulatory role of dopaminergic, adrenergic and cholinergic mechanisms upon the effect of nicotine were investigated. Animals were rendered dependent on morphine by subcutaneous (s.c.) injections of morphine sulfate 3 times a day for 3 days, and jumping behaviour was induced by intraperitoneal (i.p.) administration of naloxone 2 h after the tenth injection of morphine sulfate on day 4. Nicotine (0.001-2 mg/kg s.c.) caused a significant decrease in withdrawal jumping behaviour in morphine-dependent mice. The effect of nicotine was blocked by the central nicotinic antagonist mecamylamine (0.01-0.1 mg/kg i.p.) but not by the peripheral nicotinic antagonist hexamethonium (0.01 and 0.1 mg/kg i.p.) nor the muscarinic receptor antagonist atropine (2.5-10 mg/kg i.p.). The dopamine receptor antagonist SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5- phenyl-1H-3-benzazepine-7-ol maleate) (0.01-0.5 mg/kg s.c.) reduced the response induced by nicotine. The dopamine receptor antagonist sulpiride (25 and 50 mg/kg s.c.) and the adrenoceptor antagonists phenoxybenzamine (5 and 10 mg/kg i.p.) and propranolol (5 and 10 mg/kg i.p.) were without an effect. The results indicate that the effect of nicotine on naloxone-induced jumping is mediated by central nicotinic receptors.

Animals↗

PubMed1996

Effects of nicotine on memory retrieval in mice.

The effect of nicotine was tested on retrieval 24 h after training on a passive avoidance task. Intraperitoneal (i.p.) injection of nicotine (0.25-1.5 mg/kg) increased the step-down latency in mice dose dependently. Pretreatment with the nicotinic receptor antagonist mecamylamine (0.5-1 mg/kg) decreased, whereas pretreatment with the dopamine D1 receptor antagonist SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepine-7-ol maleate) (0.01, 0.05 and 0.1 mg/kg) and the beta-adrenoreceptor antagonist propranolol (10 mg/kg) increased the nicotine response. The dopamine receptor D2 receptor antagonist sulpiride (5-10 mg/kg), the anti-muscarinic agent atropine (2.5-10 mg/kg), the peripheral nicotinic receptor antagonist hexamethonium (0.01-0.5 mg/kg), the alpha-adrenoceptor antagonist phenoxybenzamine (1 and 10 mg/kg) and the peripheral dopamine D2 receptor antagonist domperidone (5 and 10 mg/kg) did not change the response induced by nicotine. Single administration of the antagonists did not cause response; however, a high dose of domperidone (10 mg/kg) and propranolol alone increased the step-down latencies. It may be concluded that a nicotinic receptor mechanism is involved in the nicotine-induced improvement of memory retrieval.

Animals↗

PubMed1996

Nicotine potentiates morphine antinociception: a possible cholinergic mechanism.

The effect of nicotine on morphine induced antinociception was studied using the tail-flick test. A low dose of nicotine (0.0001 mg/kg) which did not induce any antinociception, potentiated the morphine antinociceptive response dose-dependently. The opioid antagonist naloxone decreased the response of morphine and morphine plus nicotine. The muscarinic receptor antagonist atropine decreased the nicotine-induced potentiation of the morphine response. Sulpiride, pimozide, SCH 23390, phenoxybenzamine, propranolol, methysergide, metergoline, hexamethonium and mecamylamine did not alter the antinociception induced by nicotine and morphine. It is concluded that the potentiation of morphine-induced antinociception by nicotine may be mediated through a cholinergic mechanism.

Analgesics, Opioid↗

PubMed1996

Bupropion induces sniffing: a possible dopaminergic mechanism.

The effect of bupropion, an antidepressant drug, on sniffing behaviour was examined in rats. Animals treated intraperitoneally (i.p.) with different doses of bupropion (5-40 mg/kg) showed sniffing behaviour in a dose-related manner. Pretreatment of animals (i.p.) with the dopamine antagonists SCH 23390 (0.025-0.1 mg/kg) or sulpiride (12.5-50 mg/kg) decreased the sniffing induced by bupropion. Reserpine pretreatment (2.5 mg/kg, i.p., 18 h) alone and in combination with alpha-methyl-p-tyrosine (AMPT; 250 mg/kg, i.p.) also reduced the behaviour produced by the drug. The alpha-adrenoceptor phenoxybenzamine (5 and 10 mg/kg, i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg, i.p.) administered 60 min prior to bupropion did not affect the drug's effect on sniffing. Propranolol alone, however, induced sniffing. The antimuscarinic atropine (5 and 10 mg/kg, i.p.) administered 30 min prior to bupropion increased the bupropion response. Atropine alone induced vigorous sniffing. It is concluded that bupropion induced sniffing through a dopaminergic mechanism.

Animals↗

PubMed1996

Effect of picrotoxin on antinociception in the formalin test.

Subcutaneous injection of diluted formalin (0.25 microliter of 0.5%) caused a biphasic pain response in mice. The first phase of pain was observed during the first 5 min., while the second phase occurred 10-30 min. after formalin administration. With the formalin test, it was found that the antinociception produced by the GABA-A antagonist, picrotoxin, and the GABA-B antagonist, phaclofen, was abolished when employed in combination. The opioid antagonist naloxone and antimuscarinic atropine also decreased the picrotoxin response. However, sulpiride, SCH 23390, phenoxybenzamine and propranolol did not alter the picrotoxin response. Administration of naloxone, sulpiride and propranolol showed a pain response. The data indicate that dopaminergic and adrenergic mechanisms may not be involved in the picrotoxin antinociceptive effect. However, postsynaptic GABA-A and GABA-B may be involved in the drug effect, and involvement of opioid or cholinergic systems can not be excluded.

Animals↗

PubMed1995

Effects of adenosine receptor agonists and antagonists on physostigmine-induced yawning.

The effect of adenosine receptor agonists and antagonists on physostigmine-induced yawning was investigated in intact or cannulated rats. Intraperitoneal (i.p.) or intracerebroventricular (i.c.v.) administration of physostigmine to rats induced yawning dose dependently. I.p. or i.c.v. treatment of the animals with atropine, theophylline, 5-N-ethylcarboxamidoadenosine (NECA) or N6-cyclohexyladenosine reduced the yawning induced by i.p. injection of physostigmine. I.p. administration of theophylline decreased the yawning induced by i.c.v. injection of physostigmine. The inhibitory action of N6-cyclohexyladenosine (i.p.) also was decreased by 8-phenyltheophylline (i.p.) pretreatment. It is concluded that yawning induced by a central cholinergic mechanism and a central adenosine mechanism interacts with the cholinergic-induced behaviour.

Adenosine↗

PubMed1995

Effects of 5-HT receptor antagonists on morphine-induced tolerance in mice.

The effect of 5-HT receptor antagonists on tolerance to morphine antinociception was studied in mice. Slow release morphine suspension was injected subcutaneously (s.c.) in order to produce tolerance. When different doses of morphine (3, 6 and 9 mg/kg) were administered on the 4th day after injection of slow-release morphine suspension, tolerance to the test doses of morphine was observed. The tolerance obtained was decreased by pretreatment with the non-selective 5-HT receptor antagonist methysergide (1 and 2 mg/kg) or the 5-HT2 receptor antagonist ritanserin (1 and 2 mg/kg). When the 5-HT receptor antagonists were used on the 2nd and 3rd day after injection of slow-release morphine suspension or on the 4th day (60 min before last dose of morphine), a maximum reduction in morphine tolerance was observed on the 3rd day. Pretreatment of animals with metergoline (1 and 2 mg/kg) or mianserin (1 and 2 mg/kg) also decreased the tolerance to morphine. It may be concluded that at least a 5-HT2 receptor mechanism is involved in tolerance to morphine antinociception.

Analgesics↗

PubMed1995

Effects of adenosine agents on apomorphine-induced yawning in rats.

In the present work, adenosine agonists and antagonists on apomorphine-induced yawning in rats was investigated. Subcutaneous (SC) injection of apomorphine (0.02, 0.05 and 0.1 mg/kg) induced dose-dependent yawning behaviour in rats. Intracerebroventricular (ICV) administration of different doses of the drug (1, 3, 5 micrograms/rat) also caused a dose-related yawning. ICV administration of the adenosine receptor agonists 5-N-ethylcarboxamidoadenosine (NECA) and N6-cyclohexyladenosine (CHA) decreased apomorphine-induced yawning. The response induced by the adenosine agonists was reduced by 8-phenyladenosine (8-PT) pretreatment. The yawning induced by SC and ICV administration of apomorphine was decreased by ICV or IP injection of theophylline, respectively. It is concluded that at least A1 adenosine receptors may exert negative influence on the apomorphine-induced yawning. However, the exact mechanism(s) of adenosine receptors in this behaviour remain to be established.

Adenosine↗

PubMed1995

Effects of GABAergic drugs on physostigmine-induced yawning in rats.

In the present work the effects of GABA agonists and antagonists on yawning induced by physostigmine have been studied. Intraperitoneally (IP) injection of physostigmine (0.05-0.3 mg/kg) induced dose-related yawning in rats. The maximum yawning response was observed with 0.2 mg/kg of the drug. The GABA agonists muscimol (1-4 mg/kg) and baclofen (0.125-1 mg/kg) decreased yawning induced by physostigmine (0.2 mg/kg) dose dependently. Combination of both GABA agonists elicited greater inhibition of yawning. The GABA-A antagonists bicuculline or picrotoxin but not the GABA-B antagonist phaclofen reduced the inhibitory response induced by muscimol, whereas phaclofen but not bicuculline or picrotoxin reduced baclofen's inhibitory effect. Administration of bicuculline, picrotoxin or phaclofen also decreased the yawning induced by physostigmine. However, when the GABA-A and GABA-B antagonists were employed in combination, the inhibitory responses of both drugs were lost. It is concluded that GABA-A and/or GABA-B receptor stimulation may inhibit physostigmine-induced yawning.

Animals↗

PubMed1995

Effects of high doses of theophylline on memory acquisition.

Intraperitoneal (IP) injection of high doses of theophylline decreased memory acquisition dose dependently. Low but not high doses of the dopamine receptor D2 antagonist sulpiride and the dopamine D1 receptor antagonist SCH 23390 decreased the theophylline response. Pimozide and the beta-adrenoreceptor propranolol also decreased the drug response. The anti-muscarinic agent atropine, the alpha-adrenoceptor phenoxybenzamine and the 5-HT antagonist metergoline did not affect the response induced by theophylline. It is concluded that dopamine and beta-adrenergic receptor mechanisms may be involved in the theophylline-induced attenuation of memory acquisition.

Adrenergic Antagonists↗

PubMed1995

Effects of adenosine drugs on apomorphine-induced licking in rats.

1. In the present work, the effect of adenosine agonists and antagonists on apomorphine-induced licking has been studied. 2. Subcutaneous (s.c.) injection of apomorphine (0.125, 0.25 and 0.5 mg/kg) produced dose-dependent licking in rats. 3. Adenosine agonists 5'-N-ethylcarboxamide-adenosine (NECA) and N6-cyclohexyladenosine (CHA) decreased or increased the apomorphine response respectively. 4. Adenosine antagonists theophylline and 8-phenyltheophylline (8-PT) decreased the response induced by apomorphine. Potentiation of licking induced by CHA was decreased by 8-PT pretreatment. 5. It is concluded that adenosine receptors may be involved in the licking behaviour.

Adenosine↗

PubMed1995

Effects of adenosine analogues on apomorphine-induced penile erection in rats.

1. In the present work, the effect of adenosine agonists and antagonists on apomorphine-induced penile erection (PE) has been studied. 2. Subcutaneous (s.c.) injection of the nonselective D1/D2 dopamine receptor agonist apomorphine (0.05-0.5 mg/kg) induced PE in a biphasic manner. The maximum effect was obtained with 0.1 mg/kg of the drug. The response decreased with increasing doses of apomorphine, from 0.1 to 0.5 mg/kg. 3. Intraperitoneal (i.p.) injections of adenosine agonists 5'-N-ethylcarboxamidoadenosine (NECA) and N6-cyclohexyladenosine (CHA) decreased the response of apomorphine. Apomorphine-induced PE was increased by low doses (25, 50 mg/kg, i.p.) and decreased by high doses (75, 100 mg/kg, i.p.) of the adenosine antagonist theophylline, respectively. Inhibition of PE induced by NECA and CHA was antagonized by 8-PT pretreatment. 4. Intracerebroventricular (i.c.v.) administration of CHA, NECA, and theophylline produced the same effects as i.p. injections of these agents on PE responses. It is concluded that A-1 and A-2 adenosine receptor activation may inhibit PE induced by dopaminergic mechanism(s), which can be prevented by 8-PT pretreatment.

Adenosine↗

PubMed1995

Effects of cholecystokinin receptor agonist and antagonists on morphine dependence in mice.

In the present study, the effect of cholecystokinin agonists and antagonists on dependence to morphine in mice has been investigated. Mice were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily for 2-4 days, and a last dose of morphine (50 mg/kg) was administered on day 3, 4 or 5. Withdrawal syndrome (jumping) was precipitated by naloxone (2.5, 5 and 10 mg/kg) which was administered intraperitoneally 2 hr after the last dose of morphine. To study the effects of cholecystokinin receptor agonists or antagonists, 10 injection of morphine (3 administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. Cholecystokinin-8 (0.001-0.01 mg/kg), low doses of the cholecystokinin agonists caerulein (0.00001 and 0.0001 mg/kg) and, unsulfated cholecystokinin (but not high doses) as well as the antagonists MK-329 (0.5-1 mg/kg) and L-365,260 (0.5-1 mg/kg) elicit reduction of the nalaxone-induced jumping. The inhibition of jumping induced by caerulein was reduced with the selective cholecystokinin antagonists MK-329 and L-365,260. It is concluded that cholecystokinin mechanism(s) may be involved in morphine dependence, that the agonists may act on a presynaptic receptors and that the antagonists may work on postsynaptic receptors.

Animals↗

PubMed1994

On the mechanisms by which theophylline changes core body temperature in mice.

In the present work, the effects of neurotransmitter antagonists on theophylline-induced changes in body temperature were investigated. Intraperitoneal (i.p.) administration of a low dose of theophylline (25 mg/kg) induced slight hyperthermia, while high doses (75 and 100 mg/kg) induced hypothermia. The hypothermic effect of theophylline was decreased by pretreatment of animals with the dopamine D2 receptor antagonists sulpiride (15 and 30 mg/kg i.p.) and pimozide (0.125 and 0.25 mg/kg i.p.), the muscarinic receptor antagonist atropine (2.5 and 5 mg/kg i.p.) and the 5-HT receptor antagonist metergoline (0.25 mg/kg i.p.). However, the dopamine D1 receptor antagonist SCH 23390 (0.05 and 0.5 mg/kg i.p.), the alpha-adrenoceptor antagonist phenoxybenzamine (2.5 and 5 mg/kg i.p.) and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg i.p.) did not after the theophylline response. In reserpinized mice, theophylline caused a dose-dependent rise in body temperature. The response was blocked in animals pretreated with phenoxybenzamine, propranolol and atropine. Single treatment of animals with either SCH 23390 or sulpiride, and also with a combination of the two drugs, decreased the hyperthermia induced by theophylline in reserpinized mice. Pimozide or metergoline did not have any effect in this respect. These data suggest that the hypothermic response to theophylline may be mediated through dopaminergic, cholinergic and serotonergic mechanisms. The hyperthermic action of theophylline in reserpinized animals may be mediated through dopaminergic, cholinergic and adrenergic systems. Overall it seems likely that theophylline interacts with modulatory mechanisms involved in thermoregulation.

Animals↗

PubMed1994

Effects of adenosine receptor agonists and antagonists on acquisition of passive avoidance learning.

A series of experiments examined the effect of the adenosine receptor agonists N(6)-cyclohexyladenosine (CHA), N(6)-phenylisopropyladenosine (R-PIA) and 5'-N-ethylcarboxamidoadenosine (NECA); the adenosine receptor antagonists theophylline, caffeine and 8-phenyltheophylline (8-PT), and the adenosine uptake inhibitor dipyridamole on acquisition of a single trial passive avoidance learning by mice. The adenosine receptor agonists CHA (0.05, 0.1, 0.2 and 0.4 mg/kg) and R-PIA (0.00625, 0.125, 0.25 and 0.5 mg/kg) administered 1 h before the training session decreased retention dose dependently while the other adenosine receptor agonist NECA (0.0025, 0.005 and 0.01 mg/kg) had no effect. The response induced by the adenosine receptor agonists CHA and R-PIA was attenuated by the pretreatment of animals with low doses of the adenosine receptor antagonists 8-PT (2.0 mg/kg) and theophylline (25 mg/kg) but not with higher doses of the antagonists. The higher doses of the antagonists decreased the passive avoidance. Dipyridamole (7.5, 15, 30, 60 and 120 mg/kg) showed no significant effect. It is concluded that adenosine A1 receptor activation decreases the acquisition of a passive avoidance response.

Adenosine↗

PubMed1994

CCK receptor activation may prevent tolerance to morphine in mice.

Different groups of mice were treated with morphine (50 mg/kg s.c.) once daily for 1, 2, 3, 4 or 5 days, in order to develop tolerance to the drug. The antinociceptive effect of morphine (9 mg/kg s.c.) was tested 24 h after each dose of the drug administration. Tolerance to morphine reached its peak on the 4th day. Daily pretreatment of animals for a period of 4 days with different doses of cholecystokinin octapeptide (CCK-8; 0.001, 0.01, 0.05 and 0.1 mg/kg s.c.), caerulein (0.0001, 0.001, 0.005 and 0.01 mg/kg s.c.) but not unsulfated cholecystokinin octapeptide (0.001, 0.01 or 0.1 mg/kg s.c.) 30 min before daily administration of morphine (50 mg/kg s.c.) prevented the development of tolerance. A group of animals received a single dose of caerulein (0.005 mg/kg), CCK-8 (0.01 mg/kg) or unsulfated CCK-8 (0.01 mg/kg) 30 min before morphine injection (50 mg/kg s.c.) on the 3rd or 4th day. In these animals, which were tested for antinociception on the 5th day, tolerance to the drug (3, 6 and 9 mg/kg s.c.) was also decreased by caerulein, CCK-8 but not unsulfated CCK-8. In a group of mice in which peptides were administered 30 min prior to the doses of morphine (3, 6 or 9 mg/kg s.c.) on the 5th day, similar results were obtained. The results of the present study indicate that activation of both CCKB and CCKA receptors may prevent the development of tolerance to morphine, and the sulfate group in the CCK-8 molecule may be essential for the tolerance inhibition.

Analgesics↗

PubMed1994

Effects of GABA-ergic drugs on penile erection induced by apomorphine in rats.

The effects of GABA agonists and antagonists on penile erection (PE) induced by apomorphine were investigated in rats. Subcutaneous (SC) administration of apomorphine (0.01-0.1 mg/kg) induces a dose-dependent PE in rats. The maximum effect was obtained with 0.1 mg/kg of the drug. The response was decreased with increasing doses of apomorphine from 0.1 to 0.5 mg/kg. The response induced by apomorphine (0.1-0.5 mg/kg) was decreased in animals pretreated with either the GABA-A agonist muscimol or the GABA-B agonist baclofen. Combination of muscimol with baclofen caused a stronger inhibitory effect on apomorphine-induced PE. Bicuculline or picrotoxin but not phaclofen reduced the inhibitory effect of muscimol on PE induced by apomorphine, whereas phaclofen but not GABA-A antagonists decreased the inhibitory action of baclofen on apomorphine-induced PE. Pretreatment of animals with higher doses of the GABA-A antagonists bicuculline and picrotoxin or the GABA-B antagonist phaclofen elicited inhibition of apomorphine-induced PE. However, the inhibitory effects of GABA-A and GABA-B antagonists are lost on combination. Administration of GABA-A and GABA-B receptor stimulation inhibit PE induced by dopaminergic mechanism(s).

Animals↗

PubMed1994

Different influences of adenosine receptor agonists and antagonists on morphine antinociception in mice.

1. Subcutaneous (s.c.) administration of morphine to mice induced a dose-dependent antinociception. 2. Pretreatment of animals with adenosine receptor antagonists NECA (5'-N-ethylcarboxamide-adenosine) and L-PIA (N6-phenylisopropyladenosine) potentiated, while adenosine agonist CHA (N6-cyclohexyladenosine) decreased the morphine response. 3. Adenosine antagonist theophylline decreased, but adenosine receptor antagonist 8-PT (8-phenyltheophylline) increased the antinociception effect of morphine. Inhibitory effect of CHA on morphine antinociception was also reversed by 8-PT pretreatment. 4. NECA or L-PIA induced a high degree of antinociceptive effect in animals pretreated with 8-PT. 5. Dipyridamole pretreatment did not alter the effect of morphine. 6. It is concluded that A-1 and/or A-2 adenosine receptors are involved in morphine antinociception and the adenosine mechanism(s) may exert a modulatory role in this respect.

Adenosine↗