M.A. Carino

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.

Low-level microwave irradiation and central cholinergic systems

Our previous research showed that 45 min of exposure to low-level, pulsed microwaves (2450-MHz, 2-microseconds pulses, 500 pps, whole-body average specific absorption rate 0.6 W/kg) decreased sodium-dependent high-affinity choline uptake in the frontal cortex and hippocampus of the rat. The effects of microwaves on central cholinergic systems were further investigated in this study. Increases in choline uptake activity in the frontal cortex, hippocampus, and hypothalamus were observed after 20 min of acute microwave exposure, and tolerance to the effect of microwaves developed in the hypothalamus, but not in the frontal cortex and hippocampus, of rats subjected to ten daily 20-min exposure sessions. Furthermore, the effects of acute microwave irradiation on central choline uptake could be blocked by pretreating the animals before exposure with the narcotic antagonist naltrexone. In another series of experiments, rats were exposed to microwaves in ten daily sessions of either 20 or 45 min, and muscarinic cholinergic receptors in different regions of the brain were studied by 3H-QNB binding assay. Decreases in concentration of receptors occurred in the frontal cortex and hippocampus of rats subjected to ten 20-min microwave exposure sessions, whereas increase in receptor concentration occurred in the hippocampus of animals exposed to ten 45-min sessions. This study also investigated the effects of microwave exposure on learning in the radial-arm maze. Rats were trained in the maze to obtain food reinforcements immediately after 20 or 45 min of microwave exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

60 Hz magnetic fields and central cholinergic activity: Effects of exposure intensity and duration

In previous research, we have found that acute exposure to a 60 Hz magnetic field caused a decrease in cholinergic activity in the frontal cortex and hippocampus of the rat. In the present study, the effects of exposure to different intensities of the magnetic field and durations of exposure were investigated. Rats were exposed to a 60 Hz magnetic field for 60 min at a flux density of either 0.5, 1.0, 1.5, or 2.0 mT. A significant decrease in cholinergic activity was observed in the frontal cortex and hippocampus immediately after exposure to the 2.0 mT field. No significant effect was observed at lower intensities. In another experiment, effect of exposure to a 1.0 mT magnetic field for 30, 45, 60, and 90 min was investigated. A decrease in cholinergic activity was found in both brain areas after 90 min of exposure. No significant effect was observed after shorter durations of exposure. In a further experiment, the exposure duration was extended to 3 h at flux densities of 0.5, 0.1, and 0.05 mT. A significant decrease in cholinergic activity was observed in the frontal cortex and hippocampus of the rat immediately after exposure to all the intensities. It is concluded that the intensity and duration of exposure interact. By increasing the duration of exposure, effects can be observed at lower intensities.

Effects of thyrotropin-releasing hormone (TRH) microinjected into various brain areas of conscious and pentobarbital-pretreated rabbits

Abstract Thyrotropin releasing hormone (TRH) was administered intracerebrally into various brain regions of conscious and pentobarbitalnarcotized rabbits. In conscious animals tachypnea was observed after TRH administration into all brain regions investigated. Behavioral excitation was most pronounced after TRH administration into the cerebral cortex, caudate nucleus and hypothalamus. Hyperthermia was produced only after hypothalamic injections of TRH. In pentobarbital-narcotized rabbits TRH exerted analeptic activity (shortening of narcosis) regardless of the brain area injected, although some quantitative differences were observed. These results indicate that the analeptic effect of TRH may be initiated from various areas of the brain.

Effects of ethanol on central dopamine functions.

Abstract Apomorphine-elicited stereotypic behavior and motor activity were studied in rats given one-dose (3g/kg,p.o.) or 14 days (6g/kg/day, p.o.) of ethanol. Apomorphine-elicited stereotypic behavior was enhanced while motor activitu was not significantly affected in both the acute- and chronic ethanol-treated animals. Acute ethanol treatment did not affect but chronic treatment increased the concentration of 3 H-spiroperidol binding sites in the striatum. No significant change in binding affinity was observed.

Effects of TRH on the central nervous system of the rabbit.

Thyrotropin releasing hormone (TRH) administered intraventricularly to rabbits produces tachypnea, hyperthermia, behavioral excitation and, with larger doses, compulsive scratching. These effects of TRH were unaffected by various catecholamine and serotonin antagonists or depleting agents. When TRH was administered to pentobarbital-narcotized animals, tachypnea and rapid recovery of the righting reflex occurred. The antagonism of narcosis or sedation was evident against other barbiturates, diazepam, chlorpromazine, and reserpine, but not against morphine. Morphine actually appeared to antagonize the excitatory actions of TRH. Scopolamine pretreatment prevented the arousal from pentobarbital narcosis, but not the tachypnea or hyperthermia. TRH represents a new class of psychoactive chemical which may play a role in brain function.

Analeptic and antianaleptic effects of naloxone and naltrexone in rabbits

Abstract Naloxone (5 mg/kg), but not naltrexone, shortened the duration of anaesthesia in rabbits pretreated with pentobarbital. This analeptic effect was blocked by atropine, but not by methylatropine; it thus appears that a central cholinergic mechanism is involved. In contrast, smaller doses of both naloxone and naltrexone attenuated the arousal property of thyrotropin releasing hormone (TRH). Naloxone, but not naltrexone, also antagonized the analeptic property of d-amphetamine. In conscious animals naloxone potentiated, whereas naltrexone attenuated, the excitatory effects of TRH and d-amphetamine.

Intracerebroventricular injection of mu- and delta-opiate receptor antagonists block 60 Hz magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat

In previous research, we have found that acute exposure to a 60 Hz magnetic field decreased cholinergic activity in the frontal cortex and hippocampus of the rat as measured by sodium-dependent high-affinity choline uptake activity. We concluded that the effect was mediated by endogenous opioids inside the brain because it could be blocked by pretreatment of rats before magnetic field exposure with the opiate antagonist naltrexone, but not by the peripheral antagonist naloxone methiodide. In the present study, the involvement of opiate receptor subtypes was investigated. Rats were pretreated by intracerebroventricular injection of the mu-opiate receptor antagonist, beta-funaltrexamine, or the delta-opiate receptor antagonist, naltrindole, before exposure to a 60 Hz magnetic field (2 mT, 1 hour). It was found that the effects of magnetic field on high-affinity choline uptake in the frontal cortex and hippocampus were blocked by the drug treatments. These data indicate that both mu- and delta-opiate receptors in the brain are involved in the magnetic field-induced decreases in cholinergic activity in the frontal cortex and hippocampus of the rat.

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.

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.