Biomedical subjects

M R Zarrindast

Publications and source records attributed to M R Zarrindast.

At least 19 recordsLinked to original sources

PubMed2005

Discrepancy between effects of milligram and nanogram doses of a COX-2 inhibitor (celecoxib) on morphine state-dependent memory of passive avoidance in mice.

This experiment examined and compared the effects of pre-test administration of a selective COX-2 inhibitor (celecoxib), at the doses in the range of mg/kg and ng/kg on morphine state-dependent learning in step-down passive avoidance task in mice. Pre-training administration of 5mg/kg of morphine-impaired memory retrieval tested 24h later, which was restored by pre-test administration of the same dose of the drug. Pre-test administration of celecoxib (12.5, 25 and 50mg/kg), alone or in combination with morphine (1mg/kg) prevents morphine-induced memory impairment. Ultra-low doses (ULDs) of celecoxib (2, 10 and 50 ng/kg) produced no change in morphine-induced memory impairment. However, co-administration of nanogram doses of celecoxib with 5mg/kg of morphine in the test day prevented morphine-induced memory improvement, an action different from mg/kg doses. These findings implicate the involvement of COX-2 in memory retrieval and demonstrate that the effect of celecoxib ULD is different from that of mg/kg doses.

Analgesics, Opioid↗

PubMed2005

Effects of ultra-low doses of morphine, naloxone and ethanol on morphine state-dependent memory of passive avoidance in mice.

This experiment examined and compared the effects of pre-test administration of morphine, naloxone and ethanol, at doses in the range of milligram/kg to those of nanogram/kg, on morphine state-dependent learning in a step-down passive avoidance task in mice. Morphine (5 mg/kg) administered before training impaired retention tested 24 hours later, but when the same dose of morphine was also administered before the test, the retention was significantly restored. Pre-training administration of 10 or 20 ng/kg (i.p.) of morphine had no effect, but when co-administered with the same drug at 5 mg/kg (s.c.), it prevented significantly the memory recall improvement after the administration of morphine (5 mg/kg, s.c.) alone. In a parallel experiment, naloxone (5 mg/kg) prevented the memory recall improvement by morphine. However, the effects of naloxone at doses in the range of ng/kg were opposite to those of milligram doses of the same drug. Pre-test administration of ethanol (1 mg/kg) improved memory recall and mimicked the effects of pre-test morphine administration. At doses in the nanogram range, the effects of ethanol were opposite those of mg/kg of the drug. A review of the literature indicates that, for several drugs and chemicals, the effects of nanogram doses are the opposite of the effects of milligrams, because different doses have different sites as well as mechanisms of actions. In conclusion, from the above results one may suggest that, in determination of the dose-response of at least some drugs, the study of the effects of doses much lower than two orders of magnitude of the minimum effective dose are warranted.

Animals↗

PubMed2004

Effect of ethanol on morphine state-dependent learning in the mouse: involvement of GABAergic, opioidergic and cholinergic systems.

AIMS: We have studied the effect of acute administration of ethanol when it replaced morphine in step-down passive avoidance task on the test day and the effects of antagonists of GABAergic, opioidergic and cholinergic systems on ethanol actions. METHODS: Morphine (5 mg/kg, s.c.) was administered as pre-training and 24 h later as pre-test drug, and the latencies were measured in mice. Ethanol (0.125, 0.25, 1 and 2 g/kg, i.p.) was administered instead of pre-test morphine. Antagonists of GABAergic (bicuculline 0.5, 1 and 2 mg/kg, i.p.), opioidergic (naloxone 0.06, 0.25 and 1 mg/kg, i.p.) and cholinergic (atropine 0.625 and 1.25 mg/kg, i.p. and mecamylamine 0.5, 1 and 2 mg/kg, i.p.) systems were co-administered with ethanol (0.25 g/kg, i.p.) on the test day. Locomotor activity was measured as well. RESULTS: Pre-training morphine impaired the memory on the test day which was restored when the same dose of morphine was used as pre-test drug. All four doses of ethanol replaced pre-test morphine and enhanced the memory. This effect was prevented by all of the above antagonists. No significant changes were seen in the locomotor activity of the animals treated with ethanol or antagonists compared to the proper controls. CONCLUSIONS: GABAergic, endogenous opioidergic and cholinergic systems are involved in the memory recall improvement by ethanol when it replaced morphine on the test day. A review of the literature suggests other possibilities such as the release of intermediate neurotransmitters.

Animals↗

PubMed2004

Effects of different doses of glucose and insulin on morphine state-dependent memory of passive avoidance in mice.

RATIONALE: Behavioral effects of morphine, including its effect on memory, have been demonstrated to be influenced by glucose pretreatment. The measurement of step-down latency in passive avoidance has been used to study memory in laboratory animals. The pre-training injection of 5 mg/kg morphine impaired memory, which was restored when 24 h later the same dose of the drug was administered. OBJECTIVES: To investigate the effects of glucose and insulin alone or in combination with morphine, on pre-test day, on memory recall in mice. METHODS: The effects of different doses of glucose (50, 100, and 200 mg/kg, IP) and insulin (5, 10, and 20 IU/kg, IP) alone or in combination with morphine, have been studied in mice. The blood glucose level and locomotor activity of the animals were also measured. RESULTS: Although the administration of glucose alone showed no effect on morphine-induced memory impairment, its co-administration with morphine resulted in a significant and dose-dependent memory enhancement compared with the effects of morphine administration alone. Like glucose, the administration of different doses of insulin alone produced no change in the memory, but when the drug was co-administered with morphine, it significantly reduced morphine-induced memory retrieval. The effect of insulin was the opposite of glucose. None of the animals subjected to insulin treatment showed convulsions. CONCLUSIONS: Glucose is suggested to increase, on the test day, the morphine-induced memory enhancement by three different mechanisms: cholinergic or opioidergic modulations, or regulation of the ATP-dependent potassium channels.

Analgesics, Opioid↗

PubMed2004

GABAergic system and imipramine-induced impairment of memory retention in rats.

In this study, the influence of GABAergic agents, imipramine and their interactions on memory retention have been investigated. Intracerebroventricular (i.c.v.; 1-6 microg/rat) or intraperitoneal (i.p.; 5-40 mg/kg) injection of imipramine decreased memory retention. i.c.v. administration of GABA receptor agonists baclofen and muscimol also reduced memory retention. The combination of i.p. or i.c.v. injection of imipramine with a low dose of muscimol (1 microg/rat, i.c.v.) induced a higher decrease in memory retention. The higher dose of GABA(B) receptor antagonist CGP35348 [p-(3-aminopropyl)-p-diethoxymethyl-phosphinic acid] (10 microg/rat) increased memory retention by itself, and decreased the response induced by baclofen or imipramine. Bicuculline (1, 2 and 4 microg/rat, i.c.v.) tends to increase memory retention by itself. Furthermore, bicuculline in same doses reduced the response induced by muscimol or imipramine, but it did not show interaction with the latter drugs. It is concluded that the GABA(B) receptor mechanism is involved in memory impairment induced by imipramine.

Animals↗

PubMed2004

Influence of potassium channel modulators on morphine state-dependent memory of passive avoidance.

In a step-down passive avoidance task, the pre-training injection of 1.25-10 mg/kg of morphine impaired memory. This was restored when injection of the same dose of morphine (pre-test treatment) was repeated 24 h later (morphine state-dependent learning: morphine St-D). ATP-dependent potassium (K(ATP)) channels have been reported to be involved in several actions of morphine following mu-receptor stimulation. We have studied the effect of K(ATP) modulators and naloxone in the restoration of memory by morphine in mice. To investigate the part played by cholinergic systems in the effects of a K(ATP) antagonist (glibenclamide) on morphine St-D, we administered low doses of atropine before glibenclamide administration. Locomotor activity was also studied. Naloxone (0.06-1 mg/kg) reversed the effect of pre-test morphine administration. The effects of the K(ATP) channel blocker glibenclamide (2-18 mg/kg) were similar to those of the pre-test administration of morphine. Pre-test co-administration of glibenclamide and morphine showed no potentiation of the morphine effect. Glibenclamide alone or in combination with morphine did not affect locomotor activity. Pre-test administration of different doses of diazoxide (15-60 mg/kg), a K(ATP)-channel opener, had no effect on restoration of memory when used alone or in combination with morphine. In both cases, the locomotor activity was significantly reduced. Diazoxide blocked the effect of glibenclamide on memory recall. Low-dose atropine also prevented glibenclamide enhancement of memory recall, suggesting that this action of glibenclamide is through the cholinergic system.

Adenosine Triphosphate↗

PubMed2004

Involvement of nucleus accumbens in L-arginine-induced conditioned place preference in rats.

In the present study, the effects of intraperitoneal, intra-accumbal and intra-ventral tegmental area administration of L-arginine and N(G)-nitro-L-arginine methyl-ester (L-NAME) on conditioned place preference behavior were studied. Intraperitoneal (i.p.; 0.5, 1 and 5 mg/kg) and intra-accumbal (intra-NAc; 0.3, 1 and 3 microg/rat), but not intra-ventral tegmental area (intra-VTA; 0.3, 1 and 3 microg/rat) administrations of L-arginine produced a significant place conditioning. Similar injections of L-NAME did not produce any response. However, intraperitoneal pretreatment of the animals with L-NAME (5, 10 and 20 mg/kg), 30 min before L-arginine administration, significantly abolished the acquisition of place conditioning induced by either intraperitoneal or intra-accumbal injection of L-arginine. Moreover, injection of L-NAME (5, 10 and 20 mg/kg) on the test day did not alter the L-arginine response. The results may indicate that L-arginine induces conditioned place preference via an increase in nitric oxide (NO) in the nucleus accumbens.

Animals↗

PubMed2004

Influence of beta-adrenoceptor agonists and antagonists on baclofen-induced memory impairment in mice.

Post-training administration of different doses of baclofen (a GABAB agonist) has been shown to impair memory retention, in a step-down passive avoidance test in mice. We have studied the effects of beta-adrenergic agonists and antagonists on baclofen-induced memory impairment in mice. Dobutamine (a beta 1-agonist) or salbutamol (a beta 2-agonist) reversed the memory impairment induced by baclofen without exhibiting intrinsic actions on memory when administered alone. The administration of atenolol (a beta 1-antagonist) or propranolol (a beta-antagonist) produced a memory impairment. When co-administered with baclofen, both atenolol and propranolol exacerbated the memory impairment induced by the GABAB agonist. It is concluded that beta-adrenergic mechanisms may be involved in the modulation of memory via GABAB receptors.

Adrenergic beta-Agonists↗

PubMed2003

Morphine state-dependent learning: interactions with alpha2-adrenoceptors and acute stress.

The interactions of -adrenoceptors and acute restraint stress with morphine state-dependent memory of passive avoidance were examined in mice. Memory acquired following pre-training morphine administration (5 mg/kg, i.p.) was dose- and time-dependently retrieved by pre-test morphine; this effect was reversible by yohimbine (1 mg/kg). Pre-test clonidine (0.005-0.1 mg/kg) was also effective in restoring morphine-induced memory. Pre-training clonidine (2 mg/kg) induced an amnestic effect that was restorable by pre-test clonidine or morphine; this effect was also blocked by yohimbine. Acute pre-training stress for 2 h induced an amnestic effect that was reversible by pre-test morphine (1 and 5 mg/kg) or clonidine (0.01 and 0.1 mg/kg). Finally, acute pre-test stress could restore the impairment of memory induced by pre-training morphine. The data are suggestive of a functional interaction between -opioid, -adrenergic receptors and stress in modulating state-dependent learning and memory.

Acute Disease↗

PubMed2002

Effects of intrahippocampal injection of GABAergic drugs on memory retention of passive avoidance learning in rats.

The effect of post-training intrahippocampal injection of gamma-aminobutyric acid (GABA) receptor agonists and antagonists, immediately after a training session on memory retention of passive avoidance learning in rats, was measured in the presence and absence of physostigmine. Post-training treatments were carried out in all the experiments. The different doses of the GABAA receptor agonist muscimol (2, 4 and 6 microg/rat) decreased memory retention in rats dose-dependently. The higher response was obtained with 6 microg/rat of the drug. When the GABAA receptor antagonist bicuculline (0.5, 1, 2 and 4 microg/rat) was administered, only one dose of the drug (1 microg/rat) increased memory retention; however, the antagonist reduced the effect of muscimol. The GABAB receptor agonist, baclofen (0.25, 0.5, 1 and 2 microg/rat) also reduced memory retention in the animals. Intrahippocampal injection of lower doses of the GABAB receptor antagonist CGP35348 (P-[3-aminopropyl]-p-diethoxymethyl-phosphinic acid) (2.5, 5, 10 microg/rat) did not effect memory retention, although the higher doses of the drug (25 and 50 microg/rat) decreased memory retention. The doses of antagonist (2.5, 5 and 10 microg/rat), which did not elicit any response alone, reduced the effect of baclofen. The inhibitory response of CGP35348 was also decreased by bicuculline. In another series of experiments, physostigmine improved memory retention. The GABA receptor agonists, muscimol and baclofen, as well as the GABA receptor antagonists bicuculline and CGP35348, decreased the effect of physostigmine. Atropine decreased memory retention by itself and potentiated the response of muscimol and baclofen. It is concluded that GABAA and GABAB receptor activation may be involved in the impairment of memory retention.

Animals↗

PubMed2001

Effects of adenosine receptor agonists and antagonists on pentylenetetrazole-induced amnesia.

The effect of adenosine agents on amnesia induced by pentylenetetrazole was examined in mice. Post-training administration of pentylenetetrazole (50 and 60 mg/kg) disrupted 24-h retention of a single-trial passive avoidance task. The adenosine receptor antagonists, theophylline (2.5-25 mg/kg) and 8-phenyltheophylline (0.5-2 mg/kg), administered 30 min before and just after training at doses which did not affect retention, reduced the amnestic effect of pentylenetetrazole in a dose-dependent manner. Post-training administration of the adenosine A(1) receptor agonists, N(6)-cyclohexyladenosine (CHA, 0.1 and 0.5 mg/kg) and N(6)-phenylisopropyladenosine (R-PIA, 0.03 and 0.1 mg/kg), but not the adenosine A(2) receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA, 0.01 and 0.001 mg/kg), impaired retention. Nonamnestic doses of CHA and R-PIA potentiated the disruption induced by a lower dose of pentylenetetrazole (40 mg/kg). NECA did not induce any response in this respect. It is suggested that an adenosine A(1) receptor mechanism is involved in amnesia induced by pentylenetetrazole.

Adenosine↗

PubMed2001

Baclofen-impairment of memory retention in rats: possible interaction with adrenoceptor mechanism(s).

This study concerned the influence of adrenoceptor agonists and antagonists on baclofen-induced impairment of memory retention. Intracerebroventricular injection of baclofen (0.25--2 microg/rat) reduced memory retention in rats. The combination of different doses of baclofen with a low dose of clonidine (0.5 microg/rat) elicited a greater decrease in memory retention. Yohimbine (1 microg/rat) potentiated the response to a low dose, but decreased the response to higher doses of baclofen. Single administration of clonidine (0.5--2 microg/rat) but not yohimbine (1--4 microg/rat) itself decreased memory retention. The combination of clonidine with yohimbine did not show any interaction. The low dose of phenylephrine (0.5 microg/rat) or prazosin (0.5 microg/rat) also potentiated the inhibition of memory retention by baclofen. Phenylephrine (0.5--3 microg/rat) increased, while prazosin (0.5--2 microg/rat) decreased memory retention. The combination of the two drugs showed an interaction. It may be concluded that an adrenoceptor mechanism may interact with the memory retention impairment induced by baclofen.

Adrenergic alpha-Agonists↗

PubMed2001

The possible cross-tolerance between morphine- and nicotine-induced hypothermia in mice.

In the present study, cross-tolerance between hypothermia induced by morphine and nicotine in mice has been investigated. Different doses of morphine or nicotine induced dose-dependent hypothermia. The sub-maximal doses of both drugs were used for interaction studies. Administration of mecamylamine either intracerebroventricularly (2-6 microg/animal icv) or intraperitoneally (0.5 and 1 mg/kg ip) decreased both morphine- or nicotine-induced hypothermia. Naloxone either intracerebroventricularly (2-6 microg/animal) or intraperitoneally (1 and 2 mg/kg) reduced the response to morphine, but not nicotine's response. Hexamethonium (5 and 10 mg/kg ip) caused a slight decrease in morphine's hypothermia, but not that of nicotine. Nicotine's response was decreased in the animals which were made tolerant to hypothermic effect of morphine. Pre-treatment of the animals with low doses of morphine (12.5 or 25 mg/kg), once daily for 3 days, did not cause significant tolerance to the hypothermic response to morphine or nicotine. However, the administration of low doses of morphine (12.5 or 25 mg/kg) plus nicotine (2 mg/kg), once daily for 3 days, increased levels of tolerance to hypothermia induced by either drug. It is concluded that nicotinic receptor mechanism may play a role in morphine-induced hypothermia and there is cross-tolerance between the two drugs.

Animals↗

PubMed2001

Modified synthesis of 11-[14C]-clozapine.

The reported synthetic pathway of 8-chloro-11-(4-methyl-1-piperazinyl)-11-[14C]-5H-dibenzo[b,e][1,4]diazapine (clozapine) was modified in several steps. The synthetic pathway was shortened by 60% and the total yield was increased from 6% to 23%.

Journal Article↗

PubMed2001

GABA mechanisms and antinociception in mice with ligated sciatic nerve.

In the present study, the effects of GABA (gamma-aminobutyric acid) receptor agonists and antagonists on hyperalgesia induced by sciatic nerve ligation was investigated in mice. The response to morphine or GABA receptor agonists was examined 14 days after unilateral nerve ligation by hot-plate test. Intraperitoneal injection of different doses of morphine (3, 6 and 9 mg/kg), muscimol (0.5, 1 and 2 mg/kg) or baclofen (1, 2.5 and 5 mg/kg) induced a dose-related antinociception in both intact and ligated mice. The response of morphine but not that of muscimol or baclofen, in nerve-ligated mice was significantly less than that induced in the intact animals. The responses induced by muscimol or baclofen in nerve-ligated animals, were reduced by bicuculline or CGP35348 [P-(3-aminopropyl)-P-diethoxymethyl-phosphinic acid], respectively. However, morphine in combination with muscimol (2 mg/kg) tends to induce higher response; the combination of the GABA receptor agonists with morphine did not show potentiation, but additive effect. The opioid receptor antagonist naloxone reduced the response induced by muscimol in nerve-ligated animals. It was concluded that although ligation of the sciatic nerve clearly reduced the analgesic effect of morphine and not that of the GABA agonists, the results nevertheless indicated that morphine and the GABA(A) agonist shared the same mechanism of action.

Animals↗

PubMed2000

Involvement of adrenergic and cholinergic systems in nicotine-induced anxiogenesis in mice.

In the present study, the effect of alpha-adrenoceptor agents on response to nicotine in an anxiety model (elevated plus-maze) in mice was investigated. Administered nicotine reduced indices of anti-anxiety behaviour (percent open-arm time (%open-arm time) and percent open-arm entries (%open-arm entry)) and increased indices of anxiety behaviour (protected stretched attention posture and percent of protected head dipping (%protected dipping)), indicating that nicotine elicits an anxiogenic response. This response to the drug was obtained 7 min but not 30 min after drug injection and with doses of 0.25 and 0.5 mg/kg. Nicotinic receptor antagonists mecamylamine (0.5 and 1 mg/kg) and hexamethonium (5 and 10 mg/kg) reduced the response induced by nicotine (0.25 mg/kg). Mecamylamine (1 mg/kg; decreased %open-arm entry and increased protected stretched attention posture) and hexamethonium (10 mg/kg; decreased %open-arm time) showed an anxiogenic-like profile. A muscarinic receptor antagonist, atropine (2.5 and 5 mg/kg), did not alter the nicotine response but elicited an anxiogenic effect by itself. The alpha(1)-adrenoceptor antagonist prazosin (0.25 and 0.5 mg/kg), but not the alpha(1)-adrenoceptor agonist, phenylephrine (4 and 6 mg/kg), reversed the nicotine effect. Single administration of phenylephrine (6 mg/kg) increased %open-arm time, while prazosin did not alter the anxiety behaviour. The alpha(2)-adrenoceptor agonist clonidine (0.001 and 0.01 mg/kg), induced complete immobility when administered in combination with nicotine. However, an alpha(2)-adrenoceptor antagonist, yohimbine (0.5 and 1 mg/kg), appeared to reverse the nicotine response, but did not show interaction with nicotine's effect. Clonidine did not elicit any effect, but yohimbine (1 mg/kg) increased %open-arm entry and %open-arm time by itself. It can be concluded that certain doses of nicotine (0.25 and 0.5 mg/kg) 7 min after their injection induce an anxiogenic effect through nicotinic mechanism(s), and that involvement of alpha(1)- but not alpha(2)-adrenoceptors in the response to nicotine seems likely.

Adrenergic alpha-Agonists↗

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↗