Biomedical subjects

M R Zarrindast

Publications and source records attributed to M R Zarrindast.

At least 55 records · Page 3Linked to original sources

PubMed1998

Effects of GABAergic drugs on physostigmine-induced improvement in memory acquisition of passive avoidance learning in mice.

1. The effect of gamma-aminobutyric acid (GABA) receptor agonists and antagonists on acquisition of a step-down passive avoidance learning in mice was measured in the presence and absence of physostigmine. 2. Intraperitoneal injection of different doses of the anticholinesterase drug physostigmine (0.1-0.3 mg/kg) increased acquisition in mice dose dependently. The maximum response was obtained with 0.3 mg/kg of the drug. Higher doses of the drug impaired acquisition of the learned response. To show the effect of the GABAergic system on acquisition, GABAA receptor agonists and antagonists were challenged against 0.2 mg/kg of physostigmine. 3. Administration of the GABAA receptor agonist muscimol but not the GABAB receptor agonist baclofen decreased the acquisition of the learned task. However, the improvement induced by physostigmine (0.2 mg/kg) was decreased by both muscimol and baclofen. A combination of both agonists caused a higher inhibitory effect on the physostigmine response. 4. Pretreatment of animals with the higher doses of GABAA receptor antagonists bicuculline and picrotoxin but not the GABAB receptor antagonist phaclofen impaired learning. Both the GABAA and GABAB receptor antagonists reduced the learning improvement induced by physostigmine. The inhibitory effects of the GABAA and GABAB receptor antagonists are lost when combined together. 5. Bicuculline, picrotoxin or phaclofen increased the impairment of learning induced by muscimol, whereas a combination of either of the antagonists with baclofen did not alter the learning. The GABAA antagonists reduced the inhibitory effect of muscimol, whereas a higher dose of phaclofen increased the inhibition of the physostigmine response induced by muscimol and baclofen on physostigmine-induced learning improvement. 6. Phaclofen decreased but a higher dose of bicuculline increased the baclofen-induced inhibition of physostigmine effect. 7. It is concluded that both GABAA and GABAB activation inhibit improvement of acquisition induced by physostigmine.

Animals↗

PubMed1998

Effects of lead exposure on licking and yawning behaviour in rats.

In the present study, effects of lead exposure on licking and yawning behaviour have been studied. The dopaminergic receptor agonist, apomorphine (0.15, 0.25 and 0.5 mg/kg), induced dose-dependent licking in rats. The maximum response was obtained with 0.5 mg/kg of the apomorphine. Lead acetate (0.05%) exposure significantly increased apomorphine-induced licking. Yawning induced by the D2 dopaminergic agonist, bromocriptine (2, 3, 4, 8 mg/kg), and the cholinergic drug, physostigmine (0.1 or 0.3 mg/kg), was significantly decreased by lead acetate (0.05%) exposure. It may be concluded that the behaviour induced by dopaminergic or cholinergic agents can be affected by lead subchronic exposure.

Animals↗

PubMed1998

Interactions between antinociception induced by cholecystokinin antagonists and GABA agonists in the tail-flick test.

In this work, the influences of cholecystokinin receptor antagonists L-365,260, MK-329 and proglumide on antinociception induced by baclofen and GABA uptake inhibitor 4,5,6,7-tetrahydroisoxazolo [4,5-c]pyridin-3-ol (THPO) in the tail flick test has been studied. Baclofen and THPO induced antinociception in the tail flick test. Morphine, and the CCK receptor antagonists, MK-329, L-365,260 and proglumide also induced antinociception. The CCK receptor antagonists potentiated antinociceptive response induced by both baclofen and THPO. It may be concluded that cholecystokinin receptor mechanism(s) may interact with antinociception induced by GABA receptor mechanism(s).

Animals↗

PubMed1998

Nicotine potentiates sulpiride-induced catalepsy in mice.

The effects of nicotine on sulpiride-induced catalepsy in mice were investigated. Sulpiride (12.5-100 mg/kg) induced a low degree of catalepsy in mice which was dose dependent. Nicotine (0.0001-1 mg/kg) caused an even lower degree of catalepsy. When the drugs were co-administered a much higher cataleptogenic response was obtained. The potentiation of the effect of sulpiride by nicotine was elicited by 0.5 mg/kg or higher doses of the drug. The central nicotinic receptor antagonist mecamylamine (1-3 mg/kg) and the peripheral antagonist hexamethonium (5 and 10 mg/kg) decreased the response induced by the combination of nicotine and sulpiride. Higher doses of the cholinoceptor antagonist atropine (10 mg/kg) also reduced the catalepsy induced by the drug combination. It is concluded that nicotine potentiates sulpiride-induced catalepsy through activation of cholinergic mechanism(s) and that the central nicotinic mechanism mediates nicotine's action.

Animals↗

PubMed1998

Nicotine-induced grooming: a possible dopaminergic and/or cholinergic mechanism.

The ability of nicotine, to induce grooming in rats was studied. Grooming was induced by i.p. injection of different doses (0.0675-0.5 mg/kg) of nicotine to rats. The effect was dose-dependent. However, the response was decreased with increasing doses of the drug from 0.25-0.5 mg/kg. Administration of the dopamine (DA) D1/D2 receptor agonist apomorphine (0.025-5 mg/kg, i.p.) also caused grooming in a dose-dependent manner. High doses of apomorphine (0.1-0.5 mg/kg, i.p.) also induced a lower degree of response. Combination of a low dose of nicotine (0.0675 mg/kg) with different doses of apomorphine did not show any interaction. However, there was an interaction between a high dose of nicotine and apomorphine. Thus, combination of a higher dose of nicotine (0.125 mg/kg) with apomorphine, reduced apomorphine-induced grooming. The muscarinic receptor antagonist atropine (5 and 10 mg/kg), peripheral nicotinic receptor antagonist hexamethonium (5 and 10 mg/kg), central nicotinic receptor antagonist mecamylamine (1 and 3 mg/kg) and D1 DA receptor antagonist SCH23390 (0.05 and 0.1 mg/kg) all decreased the response to nicotine. Atropine, mecamylamine and SCH23390 by themselves reduced spontaneous grooming. It is concluded that nicotine elicits grooming indirectly through a possible D1 dopaminergic mechanism. However, muscarinic and nicotinic cholinergic mechanism(s) may be involved.

Animals↗

PubMed1997

Effect of adenosine receptor agonists and antagonists on morphine-induced catalepsy in mice.

Effects of adenosine receptor agonists and antagonists on morphine-induced catalepsy in mice were investigated. The adenosine agonists, NECA (5'-N-ethylcarboxamidoadenosine) and S-PIA (S(+)-N6-(2-phenylisopropyl)adenosine) in doses which did not induce any response, increased the cataleptogenic effect produced by morphine. However, the morphine response was decreased and increased by the lower and higher doses of the adenosine receptor agonist, CHA (N6-cyclohexyladenosine), respectively. The adenosine receptor antagonist, theophylline, decreased, but 8-phenyltheophylline increased, the response induced by morphine. Naloxone inhibited the catalepsy induced by morphine or morphine + NECA but not that induced by NECA alone. It is concluded that adenosine A2 receptor activation increases, while adenosine A1 receptor stimulation decreases, the morphine cataleptogenic response. The response to morphine may be mediated through opioid and adenosine receptor mechanisms.

Adenosine-5'-(N-ethylcarboxamide)↗

PubMed1997

Adenosine A3 receptor activation produces nociceptive behaviour and edema by release of histamine and 5-hydroxytryptamine.

This study evaluated the pain enhancing properties of the adenosine A3 receptor agonist N6-benzyl-5'-N-ethylcarboxamidoadenosine (N6-benzyl-NECA) by assessing behavioural effects following s.c. administration alone to the dorsal hindpaw of the rat, or in combination with a low concentration of formalin (0.5%). Edema formation was monitored by determining paw volume with plethysmometry. N6-benzyl-NECA (0.005-10 nmol) produced a dose-related increase in intrinsic flinching behaviours, as well as an increase in phase 2A flinch responses in the presence of formalin. Intrinsic effects were blocked by the histamine H1 receptor antagonist mepyramine and the 5-hydroxytryptamine2 (5-HT2) receptor antagonist ketanserin, but not by other 5-HT receptor antagonists or adenosine A1 or A2 receptor antagonists. N6-benzyl-NECA also produced an increase in paw volume, both alone and in the presence of formalin, with higher doses being required to produce this effect than for the flinch response. The increase in paw volume was also blocked by mepyramine and ketanserin but not by other antagonists. These results indicate both a nociceptive response and a proinflammatory response resulting in edema formation following activation of adenosine A3 receptors which is mediated by both 5-HT and histamine released most likely from mast cells.

Animals↗

PubMed1997

Effects of monoamine receptor antagonists on nicotine-induced hypophagia in the rat.

(--)-Nicotine, in doses of 0.2-0.6 mg/kg intraperitoneally (i.p.), induced a dose-dependent anorexia 1 h, 2 h and 4 h after food presentation in 20-h food-restricted male rats. The anorectic response of nicotine (0.4 mg/kg, 30 min before the test) was prevented by pretreatment with the central nicotine receptor antagonist mecamylamine (0.5 and 1 mg/kg). The peripheral nicotine receptor antagonist hexamethonium (5 and 10 mg/kg), the muscarinic receptor antagonist atropine (5 and 10 mg/kg), the dopamine D2 receptor antagonist pimozide (0.5 and 1 mg/kg), the dopamine D1 receptor antagonist SCH23390 (R-(+)-8-chloro-2, 3, 4, 5-tetrahydro-3-methyl-5-phenyl-1 H-3-benzazepine-7ol maleate; 0.05 and 0.1 mg/kg), the alpha-adrenoceptor antagonist phenoxybenzamine (5 and 10 mg/kg), and the beta-adrenoceptor antagonist propranolol (5 and 10 mg/kg) amplified the nicotine response while promoting anorexia by themselves. The dopamine D2 receptor antagonist sulpiride (25, 50 and 100 mg/kg) increased food intake and amplified the anorectic effect of nicotine. The 5-HT receptor antagonists metergoline (0.5 and 1 mg/kg) and mianserin (1 and 2 mg/kg) increased the nicotine effect. When the antagonists were used alone, metergoline did not change food intake, while mianserin increased food intake. It can be concluded that part of nicotine-induced anorexia is mediated through central nicotinic receptors.

Adrenergic Antagonists↗

PubMed1997

Effects of caerulein and CCK antagonists on tolerance induced to morphine antinociception in mice.

Different groups of mice received one daily dose (50 mg/kg) of morphine subcutaneously (SC) for 3, 4 or 5 days to develop tolerance to the opioid. The antinociceptive response of morphine (9 mg/kg) was tested in the hot-plate test 24 h after the last dose of the drug. Tolerance to morphine was obtained in all groups. The group of mice that received morphine for 4 days was employed for the rest of the experiments. Pretreatment of animals with a single dose of caerulein (0.025, 0.05, and 0.1 mg/kg, SC) 30 min prior to receiving morphine (50 mg/kg; during the development of tolerance to the opioid) on day 1, 2, 3, 4 or 5 of morphine administration potentiate antinociception induced by morphine (test dose of 9 mg/kg). The dose of 0.05 mg/kg of caerulein, used 30 min before morphine administration on day 3, was also used to evaluate the effects of antagonists on caerulein-induced decrease in tolerance. The selective cholecystokinin (CCK) receptor antagonists, MK-329 [1-methyl-3-(2 indoloyl)amino-5-phenyl-3H-1,4-benzodiazepin-2-one; 0.25 and 0.5 mg/kg] or L-365,260 [3R(+)-N-(2,3-dihydro-1-methyl-2-oxo-5-phenyl-1H- 1,4-benzodiazepin-3-yl)-N-(3-methyl-phenyl)urea: 0.25 and 0.5 mg/kg] decreased potentiation of morphine response induced by caerulein. MK-329 or L-365,260, when were injected 35 min before morphine injection during the development of tolerance and on day 3, decreased the tolerance to morphine. A single administration of MK-329 or L-365,260 (in the absence of caerulein) 35 min and 48 h before the test dose of morphine (9 mg/kg) potentiated the antinociception of morphine in nontolerant animals. In conclusion, CCK mechanism(s) may interact with morphine tolerance.

Analgesics, Opioid↗

PubMed1997

Caerulein may potentiate morphine-induced antinociception by cholecystokinin-A and/or cholecystokinin-B receptor mechanisms.

1. The effects of a cholecystokinin agonist and antagonist on morphine antinociception in the tail-flick test have been evaluated. 2. The administration of different doses of caerulein (0.01, 0.05 and 0.1 mg/kg) 30 min prior to morphine (1.5, 3 and 6 mg/kg) increased the antinociception induced by morphine in mice. 3. In animals pretreated with cholecystokinin antagonists MK-329 (0.125 and 0.25 mg/kg) and L-365,260 (0.125 and 0.25 mg/kg), the antinociceptive effect of morphine was not changed. However, high doses (0.5 mg/kg) of each antagonist potentiated the morphine response. 4. Low doses of cholecystokinin antagonists (0.125 and 0.25 mg/kg), that did not cause antinociception, when employed in combination with caerulein (0.05 mg/kg) decreased the response of morphine plus caerulein. 5. It is concluded that the cholecystokinin agonist caerulein potentiated the morphine response by stimulation of cholecystokinin-A and/or cholecystokinin-B receptors.

Analgesics, Opioid↗

PubMed1997

Adenosine receptor agents and conditioned place preference.

1. The effects of different doses of the adenosine agonists N5-ethylcarboxamido-adenosine (NECA), R-isomer of N6-phenylisopropyladenosine (R-PIA), and N6-cyclohexyladenosine (CHA) or of the antagonists theophylline and 8-phenyltheophylline (8-PT) on conditioned place preference (CPP) have been studied. 2. The results show that R-PIA and CHA induced conditioned place aversion (CPA) whereas NECA induced conditioned place preference (CPP). 3. Low doses of theophylline elicit CPP, but high doses of the drug induced CPA. 8-PT also produced the CPP. 4. The responses of R-PIA and CHA but not NECA was decreased by theophylline and 8-PT administration. 5. It is concluded that the induction of CPP an CPA by adenosine antagonsists may be mediated by different adenosine receptors.

Adenosine↗

PubMed1997

Involvement of GABAB receptors in the antinociception induced by baclofen in the formalin test.

1. The effect of GABA receptor antagonists on baclofen-induced antinociception was examined in rats using the formalin test. Intraperitoneal (IP) administration of different doses of baclofen (2.5-10 mg kg-1) to rats induced antinociception in both phases of the test. 2. The response was dose-dependent and the maximum response was observed with 10 mg kg-1 of the drug. Intracerebroventricular (ICV) injection of baclofen (0.5-20 micrograms/rat) also induced dose-dependent antinociception in the second phase of the formalin test. 3. The GABAB antagonist, phaclofen (1 mg kg-1, IP) but not the GABAA antagonists picrotoxin (1 mg kg-1, IP) and bicuculline (1.5 mg kg-1, IP), decreased the antinociception induced by both ICV and IP administration of baclofen. 4. It is concluded that baclofen antinociception in the formalin test is mediated through GABAB receptor activation.

Animals↗

PubMed1997

Effects of lead exposure on bromocriptine-induced penile erection in rats.

In the present work we have studied the effects of lead exposure on penile erection induced by bromocriptine. Intraperitoneal injection of bromocriptine (2, 3, 4 and 8 mg/kg) induced dose-related penile erection in rats. Maximum response was observed with 4 mg/kg of the drug. Lead exposure (as Pb-acetate in drinking water) for periods of 7, 14, 21 and 28 days decreased the bromocriptine-induced penile erection response. Higher concentrations of lead (0.05%) were shown to cause a more prominent decrease of penile erection. The same procedure for lead administration did not significantly alter penile erection induced by physostigmine (0.1 and 0.3 mg/kg, intraperitoneally). In a series of experiments, blood lead concentrations were measured 7 and 21 days after lead exposure. Significant increases of lead concentrations were found after lead exposure. It is concluded that lead can influence bromocriptine-induced penile erection.

Animals↗

PubMed1997

On the mechanism(s) of cholecystokinin (CCK): receptor stimulation attenuates morphine dependence in mice.

In the present study, effect of cholecystokinin (CCK) agonists and on dependence to morphine in mice has been investigated. The influence of dopaminergic, adrenergic, cholinergic and serotonergic on attenuation of naloxone-induced jumping in morphine-dependent mice by CCK agonists were also considered. Mice were treated subcutaneously with morphine (50, 50 and 75 mg/kg) three times daily (10 a.m. 1 p.m. and 4 p.m.) for 3 days, and a last dose of morphine (50 mg/kg) was administered on the 4th day. Withdrawal syndrome (jumping) was precipitated by naloxone (5 mg/kg) which was administered intraperitoneally 2 hr after the last dose of morphine. To study effects of CCK receptor agonists, 10 injection of morphine (3 administrations each day) for dependence and a dose of 5 mg/kg of naloxone for withdrawal induction were employed. The CCK agonists CCK-8 (0.001-0.1 mg/kg), unsulfated CCK-8 (CCK-8U; 0.001-0.1 mg/kg) and caerulein (0.00001-0.01 mg/kg) were able to prevent withdrawal signs precipitated by naloxone (5 mg/kg). Sulpiride and pimozide increased response induced by CCK-8 agonists. The dopamine antagonists also attenuates jumping by themselves. SCH 23390 did not alter the CCK-8 effect, but decreased the jumping by itself. Phenoxybenzamine, propranolol, methysergide and atropine did not change the caerulein effect significantly. However, single administration of atropine increased and methysergide decreased jumping. It is concluded that CCK mechanism(s) may be involved in morphine dependence, and dopaminergic mechanism(s) may interact with CCK in attenuation of naloxone-induced jumping.

Adrenergic Antagonists↗

PubMed1997

Involvement of cholinergic and opioid receptor mechanisms in nicotine-induced antinociception.

In this work we have studied the influences of nicotinic agents on the antinociception of morphine in formalin test. Nicotine (0.001-0.1 mg/kg) induced antinociception in mice in a dose-dependent manner in the early phase of formalin test, and also potentiated the morphine effect. The nicotinic receptor antagonist, mecamylamine (0.5 mg/kg), but not hexamethonium decreased the antinociception induced by nicotine (0.1 mg/kg) in both phases. The muscarinic receptor antagonist atropine (5 and 10 mg/kg) also decreased the response of nicotine. Mecamylamine, hexamethonium or atropine did not alter morphine antinociceptive response, while naloxone decreased responses induced by nicotine or morphine. The antagonists by themselves did not elicit any response in formalin test, however, high does of mecamylamine tend to increase pain response. It is concluded that central cholinergic and opioid receptor mechanisms may be involved in nicotine-induced antinociception.

Analgesics, Opioid↗

PubMed1997

Opposite influences of different adrenoceptors on baclofen-induced antinociception in mice.

In the present study, the effects of adrenoceptor agonists and antagonists on baclofen-induced antinociception was investigated. Intraperitoneal administration of different doses of baclofen (2.5, 5 and 10 mg/kg) induced antinociception in the tail-flick test. The response was dose-dependent. The alpha 2-adrenoceptor agonist, clonidine, increased, while the alpha 1-adrenoceptor agonist, phenylephrine, decreased the baclofen response. In reserpine-treated animals, alpha 2-adrenoceptor, clonidine, induced antinociception and increased that of baclofen. Yohambine and propranolol but not prazosin decreased the baclofen effect. Although phenoxybenzamine itself induced antinociception it did not alter the baclofen response significantly. Reserpine treatment decreased the response induced by single administration of baclofen or phenoxybenzamine and that induced by a combination of baclofen with either phenoxybenzamine or prazosin. It may be concluded that alpha 2-adrenoceptor stimulation increases, while alpha 1-adrenoceptor activation decreases the baclofen-induced antinociception, and aminergic mechanism(s) may have a positive influence on baclofen response.

Adrenergic Agonists↗

PubMed1996

Effects of reversible inactivation of the medial septal area on long-term potentiation and recurrent inhibition of hippocampal population spikes in rats.

We assessed the effects of reversible inactivation of the medial septal area (MSA) on long-term potentiation (LTP) and recurrent inhibition in the dentate gyrus of urethane-anesthetized rats, in vivo. The septal input to the hippocampus was temporarily eliminated by injection of tetrodotoxin (TTX, 10 ng/l microliter) into the MSA. In Experiment 1, LTP inducibility was examined in the perforant-dentate gyrus synapses in the MSA inactivated and control rats by 2 high-frequency stimulation (HFS), 5 min apart, applied to the perforant pathway (PP). The magnitude of potentiation was evaluated as the percentage change in the population spike (PS) amplitude at 5, 30, 60 or 120 min after the second HFS. The PS amplitude in the MSA inactivated rats was significantly lower than those of control group at 120 but not 5, 30 or 60 min after the second HFS. The MSA inactivation itself had no effect on the basal responses evoked by test stimuli. In Experiment 2, the MSA inactivation did not affect the efficacy of recurrent inhibition in the perforant-dentate gyrus synapses produced by paired pulses applied to the PP at 10- and 20-ms interpulse intervals. These results indicate that: (1) although hippocampal synapses can be still potentiated after the HFS in the MSA inactivated animals, a faster decay of LTP may be due to elimination of the MSA output amplification on synaptic responses mediated by excitatory amino acids; and (2) the recurrent inhibition mechanism in the dentate gyrus of the hippocampus is not probably affected by the MSA inactivation.

Action Potentials↗

PubMed1996

Theophylline-induced grooming: possible indirect dopaminergic mechanism.

The ability of theophylline, an adenosine antagonist and phosphodiesterase inhibitor, to induce grooming was studied in rats. Grooming was induced by intraperitoneal (i.p.) injection of different doses (6-25 mg/kg) of theophylline to rats. The effect was dose-dependent. However, the response was decreased with increasing doses of the drug from 25-75 mg/kg. Administration of the dopamine D1 receptor agonist SKF 38393 (1-phenyl-7,8-dihydroxy-2,3,4,5-tetrahydro-1 H-3-benzazepine hydrochloride; 16 mg/kg i.p.) also caused grooming in a dose-dependent manner. The response induced by SKF 38393 (1-4 mg/kg i.p.) was decreased by the high doses of theophylline (50 and 75 mg/kg i.p.). The dopamine D1 receptor antagonist SCH 23390 (R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1 H-benzazepine-7-ol maleate) decreased the theophylline and SKF 38393 response. Pretreatment of animals with reserpine (2.5 mg/kg i.p., 24 h) reduced the effect of theophylline (12.5 and 25 mg/kg i.p.) but not that of SKF 38393 (1 and 4 mg/kg i.p.). It is concluded that theophylline elicits grooming through an indirect D1 dopaminergic mechanism.

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