Biomedical subjects

M A Carino

Publications and source records attributed to M A Carino.

At least 19 recordsLinked to original sources

PubMed1998

Acute exposure to a 60 Hz magnetic field affects rats' water-maze performance.

Rats were trained in six sessions to locate a submerged platform in a circular water-maze. They were exposed to a 1 mT, 60 Hz magnetic field for one hour in a Helmholtz coil system immediately before each training session. In addition, one hour after the last training session, they were tested in a probe trial during which the platform was removed and the time spent in the quadrant of the maze in which the platform was located during the training sessions was scored. Control animals were sham-exposed using the exposure system operating with the coils activated in an anti-parallel direction to cancel the fields. A group of "non-exposed" control animals was also included in the study. There was no significant difference between the magnetic field-exposed and control animals in learning to locate the platform. However, swim speed of the magnetic field-exposed rats was significantly slower than that of the controls. During the probe trial, magnetic field-exposed animals spent significantly less time in the quadrant that contained the platform, and their swim patterns were different from those of the controls. These results indicate that magnetic field exposure causes a deficit in spatial "reference" memory in the rat. Rats subjected to magnetic field exposure probably used a different behavioral strategy in learning the maze.

Animals↗

PubMed1996

Intraseptal microinjection of beta-funaltrexamine blocked a microwave-induced decrease of hippocampal cholinergic activity in the rat.

Acute (45 min) exposure to pulsed (2 microseconds pulse width, 500 pulses per second) 2450-MHz microwaves at a power density of 1 mW/cm2 (whole body specific absorption rate 0.6 W/kg) microwaves caused a decrease in cholinergic activity in the hippocampus of the rat as measured by the sodium-dependent high-affinity choline uptake. Microinjection of beta-funaltrexamine (1 microgram) into the septum before microwave exposure blocked this effect. These data indicate that mu-opioid receptors in the septum mediate a microwave-induced decrease in cholinergic activity in the hippocampus and support our hypothesis that microwaves at a whole body SAR of 0.6 W/kg can activate endogenous opioids in the brain.

Animals↗

PubMed1995

Involvement of D1 and D2 dopamine systems in the behavioral effects of cocaine in rats.

Cocaine (5-40 mg/kg, intraperitoneally) enhanced locomotion and rearing accompanied with head circling and body shaking. Although at 40 mg/kg typical stereotypy licking occasionally appeared, 40% of the rats died. At doses that did not affect physiologic locomotion and rearing, the D1-receptor antagonist SCH23390 but not D2 antagonist raclopride inhibited locomotion and rearing stimulated by cocaine (20 mg/kg). All behavioral responses of cocaine were abolished with increasing doses of raclopride and SCH23390. Sulpiride, a D2 antagonist, exerted a biphasic effect on locomotor activity (i.e., a low dose of sulpiride increased and a high dose decreased cocaine-induced locomotor activity). Sulpiride enhanced head circling, body shaking, and increases of rearing induced by cocaine. D2-receptor agonists quinpirole and bromocriptine inhibited these responses, presumably by activating the typical stereotyped behaviors such as sniffing at low doses, and licking and gnawing at high doses. The lowest dose of bromocriptine inhibited all behaviors induced by cocaine without producing typical stereotyped behaviors in itself. SK+F38393, a D1-receptor agonist, in combination with cocaine did not induce typical stereotype, which results in a synergistic effect of D1 and D2-receptor activities. The increases of locomotion and rearing, head circling, and body shaking induced by cocaine may involve the indirect activation of postsynaptic D1 and D2 receptors, presumably via dopamine release, resulting from inhibition of the presynaptic D2 receptors. These results also provide evidence that the indirect stimulation of postsynaptic D2 receptors by cocaine (20 mg/kg) is insufficient to induce stereotyped behaviors, and that the role of dopamine D1 receptors in mediating the behavioral actions of acute cocaine appears to be more important than that of D2 receptors. Our results also suggest that bromocriptine may be useful for the treatment of acute cocaine poisoning.

Animals↗

PubMed1994

The analeptic effect of methamphetamine in pentobarbital-narcotized rats is mediated via a dopaminergic-cholinergic mechanism.

Methamphetamine (MAP) administered in doses of 0.5 to 5 mg/kg i.p. to rats anesthetized with pentobarbital produced a shortening of the duration of loss of righting reflex. This analeptic effect of MAP was blocked by atropine but not by atropine methylbromide, indicating the central cholinergic nature of the response. This effect was also blocked by the D1 and D2 dopamine antagonists SCH 23390 (0.2 mg/kg) and raclopride (2 mg/kg), respectively. Pentobarbital decreased sodium-dependent high-affinity choline uptake (HACU) in frontal cortex and hippocampus as measured in synaptosomes from treated rats. MAP given to pentobarbital-narcotized rats restored HACU activity to nonanesthetized levels, but this restorative effect of MAP was blocked by SCH 23390 or raclopride. These data suggest that in addition to a cholinergic mechanism, the analeptic effect of MAP involves the dopamine system. alpha-Methyl-p-tyrosine, but not reserpine, pretreatment completely blocked the MAP analeptic response. In reserpinzed rats, MAP produced a markedly enhanced analeptic response. Studies of the effects of repeated administration of MAP on its analeptic activity were also undertaken in view of the well known sensitization to the locomotor and stereotypic effects of the amphetamines that occur with repeated intermittent administration. Rats pretreated daily with MAP (5 mg/kg) for 5 or 12 days showed neither tolerance nor sensitization to the analeptic effect of subsequent MAP administrations. 3H-quinuclidinyl benzilate-binding studies also showed no changes in muscarinic binding characteristics of membranes prepared from cortex or hippocampus of rats pretreated chronically with MAP. These and our earlier studies suggest that the analeptic effect of MAP is mediated via a dopaminergic-cholinergic mechanism.

Animals↗

PubMed1993

Effects of a 60 Hz magnetic field on central cholinergic systems of the rat.

We studied the effects of an acute (45 min) exposure to a 60 Hz magnetic field on sodium-dependent, high-affinity choline uptake in the brain of the rat. Decreases in uptake were observed in the frontal cortex and hippocampus after the animals were exposed to a magnetic field at flux densities > or = 0.75 mT. These effects of the magnetic field were blocked by pretreating the animals with the narcotic antagonist naltrexone, but not by the peripheral opioid antagonist, naloxone methiodide. These data indicate that the magnetic-field-induced decreases in high-affinity choline uptake in the rat brain were mediated by endogenous opioids in the central nervous systems.

Animals↗

PubMed1993

The effects of SCH 23390 and raclopride on cocaine-induced analepsis and EEG arousal in rabbits.

The effects of the dopamine D1 and D2 receptor antagonists on cocaine-induced, cholinergically-mediated analeptic and hippocampal theta activity in anesthetized rabbits were investigated. Cocaine (2 mg/kg, i.v.) reduced by 35% the duration of loss of righting reflex produced by a 25 mg/kg dose of pentobarbital. This shortening of narcosis time was blocked by pretreating the animals with the D1 antagonist, SCH 23390 (0.1 mg/kg) but not with the D2 antagonist raclopride (1-2 mg/kg). Cocaine (5 mg/kg, i.v.) also produced a short burst of increased hippocampal theta activity in urethane-anesthetized rabbits, which was also blocked by SCH 23390 but not by raclopride. An unexpected finding was that raclopride itself, at 2 mg/kg (i.v.), produced a marked activation of theta activity that lasted for 15-20 min. When cocaine was administered after this time it produced a potentiated theta response, both in duration and in magnitude. These results suggest that in the rabbit, cocaine exerts a cholinergically-mediated behavioral and EEG arousal through a D1 dopamine mechanism. The role of the D2 system is less clear but appears to be antagonistic to the D1-mediated response.

Analysis of Variance↗

PubMed1992

Single vs. repeated microwave exposure: effects on benzodiazepine receptors in the brain of the rat.

We studied the effects of single (45 min) and repeated (ten daily 45-min sessions) microwave exposures (2450-MHz, 1 mW/cm2, average whole-body SAR of 0.6 W/kg, pulsed at 500 pps with pulse width of 2 microseconds) on the concentration and affinity of benzodiazepine receptors in the cerebral cortex, hippocampus, and cerebellum of the rat. We used a receptor-binding assay with 3H-flunitrazepam as ligand. Immediately after a single exposure, an increase in the concentration of receptor was observed in the cerebral cortex, but no significant effect was observed in the hippocampus or cerebellum. No significant change in binding affinity of the receptors was observed in any of the brain-regions studied. In rats subjected to repeated exposures, no significant change in receptor concentration was found in the cerebral cortex immediately after the last exposure, which may indicate an adaptation to repeated exposures. Our data also show that handling and exposure procedures in our experiments did not significantly affect benzodiazepine receptors in the brain. Because benzodiazepine receptors in the brain are responsive to anxiety and stress, our data support the hypothesis that low-intensity microwave irradiation can be a source of stress.

Animals↗

PubMed1992

Opioid receptor subtypes that mediate a microwave-induced decrease in central cholinergic activity in the rat.

We performed experiments to investigate subtypes of opioid receptors in the brain involved in the effect of acute (45 min) pulsed microwave exposure (2,450-MHz, 2-microseconds pulses, 500 pps, average power density 1 mW/cm2, peak-power density, 1 W/cm2, average whole body SAR 0.6 W/kg) on cholinergic activity in the rat brain. Rats were pretreated by microinjection of specific antagonists of mu, delta, and kappa opioid-receptors into the lateral cerebroventricle before exposure to microwaves. The data showed that all three subtypes of opioid receptors are involved in the microwave-induced decrease in cholinergic activity in the hippocampus. However, the microwave-induced decrease in cholinergic activity in the frontal cortex was not significantly affected by any of the drug treatments, confirming our previous conclusion that the effect of microwaves on the frontal cortex is not mediated by endogenous opioids.

Animals↗

PubMed1992

Opioid receptor subtypes mediating the noise-induced decreases in high-affinity choline uptake in the rat brain.

Acute (20 min) exposure to 100-dB white noise elicits a naltrexone-sensitive decrease in sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. In the present study, the subtypes of opioid receptors involved were investigated by pretreating rats with microinjection of specific opioid-receptor antagonists into the lateral cerebroventricle before noise exposure. We found that the noise-induced decrease in high-affinity choline uptake in the hippocampus was blocked by pretreatment with either mu-, delta-, or kappa-opioid-receptor antagonists, whereas the effect of noise on frontal cortical high-affinity choline uptake was blocked by a mu- and delta- but not by a kappa-antagonist. These data further confirm the role of endogenous opioids in mediating the effects of noise on central cholinergic activity and indicate that different neural mechanisms are involved in the effects of noise on the frontal cortical and hippocampal cholinergic systems.

Animals↗

PubMed1991

Naltrexone pretreatment blocks microwave-induced changes in central cholinergic receptors.

Repeated exposure of rats to pulsed, circularly polarized microwaves (2,450-MHz, 2-microseconds pulses at 500 pps, power density 1 mW/cm2, at an averaged, whole-body SAR of 0.6 W/kg) induced biphasic changes in the concentration of muscarinic cholinergic receptors in the central nervous system. An increase in receptor concentration occurred in the hippocampus of rats subjected to ten 45-min sessions of microwave exposure, whereas a decrease in concentration was observed in the frontal cortex and hippocampus of rats exposed to ten 20-min sessions. These findings, which confirm earlier work in the authors' laboratory, were extended to include pretreatment of rats with the narcotic antagonist naltrexone (1 mg/kg, IP) before each session of exposure. The drug treatment blocked the microwave-induced changes in cholinergic receptors in the brain. These data further support the authors' hypothesis that endogenous opioids play a role in the effects of microwaves on central cholinergic systems.

Animals↗

PubMed1991

D1 agonist SKF 38393 antagonizes pentobarbital-induced narcosis and depression of hippocampal and cortical cholinergic activity in rats.

SKF 38393 (5 mg/kg), but not quinpirole, shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rats. This effect was blocked by atropine (2 mg/kg), but not by atropine methylbromide, suggesting involvement of central cholinergic mechanisms. The analeptic effect was also blocked by SCH 23390 (0.2 mg/kg) or raclopride (2 mg/kg). SKF 38393 also increased sodium dependent high affinity choline uptake (HACU) in cortical and hippocampal synaptosomes that had been depressed by pentobarbital. SCH 23390 or raclopride prevented the SKF 38393 reversal of the depressed HACU, indicating that both D1 and D2 mechanisms were involved mediating the analeptic effect. These results provide neurochemical evidence that cortical and hippocampal D1-mediated cholinergic activation results in a behavioral arousal (analeptic) response. They also suggest that DA mechanisms may be involved in regulation of cortical and hippocampal cholinergic neurons.

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

PubMed1991

D-1 agonist, SKF 38393, but not a D-2 agonist, produces a cholinergically mediated analeptic effect in rabbits.

SKF 38393 (2-15 mg/kg, IV), but not quinpirole, shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rabbits. This effect was blocked by atropine (2-5 mg/kg, IV), but not by atropine methylbromide, suggesting that a central cholinergic mechanism was involved. The analeptic effect was also blocked by SCH 23390 (0.1 mg/kg, IV) or raclopride (5 mg/kg, IV). These results indicate that SKF 38393 activates central cholinergic neurons, which in turn initiate the analeptic effect. However, the fact that raclopride also blocked the SKF 38393 analeptic effect, but quinpirole did not exert any analeptic effect, suggests that a D-1/D-2 modulation of cholinergic systems may be involved in the SKF 38393-induced analeptic effect. These results also support our earlier findings and view that cocaine-induced analeptic activity is mediated by a dopaminergic-cholinergic mechanism.

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

PubMed1990

Effects of noise on high-affinity choline uptake in the frontal cortex and hippocampus of the rat are blocked by intracerebroventricular injection of corticotropin-releasing factor antagonist.

Acute exposure (20 min) to loud noise (100 dB) decreased sodium-dependent high-affinity choline uptake activities in the frontal cortex and hippocampus of the rat. These effects were blocked by intracerebroventricular (i.c.v.) administration of the corticotropin-releasing factor (CRF) antagonist alpha-helical-CRF9-41 (alpha-HCRF) immediately before noise exposure. Intracerebroventricular injection of CRF (1 microgram) also decreased high-affinity choline uptake in the frontal cortex and the hippocampus of the rat, and these effects of CRF could be blocked by pretreating the animal with the narcotic antagonist naltrexone (1 mg/kg, i.p.). These results indicate that the effects of noise on central cholinergic systems are mediated by CRF and suggest a stressor-CRF-endogenous opioid-acetylcholine sequence of effects in the brain.

Acoustic Stimulation↗

PubMed1990

Acute white noise exposure affects the concentration of benzodiazepine receptors in the brain of the rat.

Rats were acutely (45 min) exposed to 100-dB white noise, and benzodiazepine receptors in the cerebral cortex, hippocampus, and cerebellum were studied immediately after exposure by the receptor-binding assay using 3H-flunitrazepam as the ligand. An increase in the concentration of receptors was observed in the cerebral cortex, whereas no significant change in receptor concentration was seen in the hippocampus and cerebellum. No significant effect of noise on receptor binding affinity was detected in the three brain regions studied. Experimental handling also did not significantly affect the benzodiazepine receptor properties. These data confirm previous reports that acute exposure to stressor can cause rapid changes in benzodiazepine receptors in the brain.

Animals↗

PubMed1990

Cocaine produces cholinergically mediated analeptic and EEG arousal effects in rabbits and rats.

Cocaine (1-5 mg/kg, IV) shortened the duration of loss of righting reflex produced in pentobarbital-narcotized rabbits. This effect was completely blocked by scopolamine (1 mg/kg, IV), but not by scopolamine methylbromide, suggesting that a central cholinergic mechanism was involved. In urethane-anesthetized rats cocaine (1 mg/kg, IV) consistently generated hippocampal EEG theta rhythm lasting about 40 min. This effect was also abolished by scopolamine. These results suggest that cocaine produced behavioral and EEG arousal responses that involved the septohippocampal cholinergic system.

Acetylcholine↗

PubMed1990

Corticotropin-releasing factor antagonist blocks microwave-induced decreases in high-affinity choline uptake in the rat brain.

Acute (45-min) irradiation with pulsed low-level microwaves (2450-MHz, 2 microseconds pulses at 500 pps, average power density of 1 mW/cm2, whole-body average specific absorption rate of 0.6 W/kg) decreased sodium-dependent high-affinity choline uptake (HACU) activity in the frontal cortex and hippocampus of the rat. These effects were blocked by pretreating the animals before exposure with intracerebroventricular injection of the specific corticotropin-releasing factor (CRF) receptor antagonist, alpha-helical-CRF9-41 (25 micrograms). Similar injection of the antagonist had no significant effect on HACU in the brain of the sham-exposed rats. These data suggest that low-level microwave irradiation activates CRF in the brain, which in turn causes the changes in central HACU.

Animals↗

PubMed1989

Repeated noise exposure affects muscarinic cholinergic receptors in the rat brain.

We examined the effect of repeated exposure to 100-dB white noise (10 daily 45-min sessions) on muscarinic cholinergic receptors in different regions of the rat brain. Twenty-four hours after the last exposure session, increase in concentration (Bmax) of [3H]quinuclidinyl benzilate ([3H]-QNB) binding sites was observed in the hippocampus, but no significant change was seen in the striatum, frontal cortex, and hypothalamus. No significant effect of noise on receptor binding affinity (Kd) was found. Pretreating the rats with naltrexone (1 mg/kg, IP) before exposure blocked the noise-induced increase in cholinergic receptors in the hippocampus.

Animals↗

PubMed1989

Low-level microwave irradiation and central cholinergic activity: a dose-response study.

Rats were irradiated with circularly polarized, 2,450-MHz pulsed microwaves (2-microseconds pulses, 500 pulses per second [pps]) for 45 min in the cylindrical waveguide system of Guy et al:(Radio Sci 14:63-74, 1979). Immediately after exposure, sodium-dependent high-affinity choline uptake, an indicator of cholinergic activity in neural tissue, was measured in the striatum, frontal cortex, hippocampus, and hypothalamus. The power density was set to give average whole-body specific absorption rates (SAR) of 0.3, 0.45, 0.6, 0.75, 0.9, or 1.2 W/kg to study the dose-response relationship between the rate of microwave energy absorption and cholinergic activity in the different areas of the brain. Decrease in choline uptake was observed in the striatum at a SAR of 0.75 W/kg and above, whereas for the frontal cortex and hippocampus, decreases in choline uptake were observed at a SAR of 0.45 W/kg and above. No significant effect was observed in the hypothalamus at the irradiation power densities studied. The probit analysis was used to determine the SAR50 in each brain area, i.e., the SAR at which 50% of maximum response was elicited. SAR50 values for the striatum, frontal cortex, and hippocampus were 0.65, 0.38, and 0.44 W/kg, respectively.

Animals↗