Dopamine D-2 receptor mediation of response suppression learning of young rats

In three experiments, the effects of augmenting or blocking dopamine (DA) D-2 receptor activity on the ontogeny of response suppression learning of preweanling rat pups were determined. In the initial experiment, rat pups were trained to traverse a straight alley for nipple attachment to an anesthetized dam. When footshock (0.2 mA, 0.5 sec) was made contingent on responding, younger (11- and 13-day-olds) rat pups were deficient to older (17- and 19-day-olds) pups at withholding punished responding. In the subsequent experiments, response suppression learning was assessed after injecting 11- and 17-day-old rat pups with the specific DA D-2 agonist, LY 171555 (0.005-, 0.01-, and 0.1-mg/kg, i.p.), or the specific DA D-2 antagonist, sulpiride (5.0-, 15.0-, and 50.0-mg/kg, i.p.). LY 171555 enhanced the punished responding of both the 11- and 17-day-old rat pups; whereas, sulpiride increased the punished responding of the 17-, but not the 11-day-olds. In four additional experiments, the effects of LY 171555 and sulpiride on the locomotor activity, nociception, and reinforcement processes of 17-day-old rat pups was assessed. Rat pups given LY 171555 (0.01 mg/kg, i.p.) exhibited enhanced locomotor activity and a trend towards hyperanalgesia using a hot plate task. Sulpiride (15.0 mg/kg, i.p.) completely antagonized LY 171555's activity enhancing effects and had hyperalgesic properties. In two experiments, sulpiride did not affect the nonpunished appetitive responding of the 17-day-olds; whereas, haloperidol-treated pups responded on fewer reinforced trials than did saline-treated pups. Therefore, these results indicate that the response suppression learning of 17-day-old rat pups is mediated, at least partially, by a DAD-2 receptor system, and that D-2 receptors are also involved in the locomotor activity and nociceptive responses of young rat pups.     

Effects of apomorphine and haloperidol on somatopetal transport of horseradish peroxidase in the nigro-striatal pathway

Labeling of cell bodies in pars compacta of substantia nigra (SNc) following injections of horseradish peroxidase (HRP) in the neostriatum was not affected by repeated systemic injections of apomorphine or haloperidol during the survival time. These drugs decelerate and accelerate, respectively, the firing of SNc neurons. Provided the used standard method was sensitive enough, it could be concluded that at least in these neurons the somatopetal transport and accumulation of the tracer do not depend on the rate of electrical activity. Consequently, the intensity of labeling with HRP is not a sensitive index of neuronal activity.     

Effects of apomorphine on sexual behavior in young and middle-aged rats

Apomorphine (APO), the prototypical dopamine agonist, produced different effects on the copulatory patterns of sexually vigorous male rats depending on the dose, the time between treatment and behavioral observation and the age of the animals. Prior to any drug treatment, middle-aged males (13 months of age) exhibited prolonged latencies to ejaculation and intervals between intromissions when compared to young male rats (3 months of age). In mating tests to young male rats initiated six minutes after treatment, administration of low doses of APO was followed by reductions in the ejaculatory threshold (0.05-0.8 mg/kg). The greatest reduction in the ejaculatory threshold was observed after administration of 0.4 mg/kg APO. No such facilitation of ejaculatory behavior was evident in the middle-aged males. Age-related differences in APO-induced changes in ejaculation latency (0.05-0.8 mg/kg), intromission frequency (0.05-0.4 mg/kg), copulatory efficacy (0.2 and 0.8 mg/kg) and intercopulatory interval (0.8 mg/kg) were evident. Doses of APO above 0.4 mg/kg in young males and above 0.2 mg/kg in middle-aged males elicited dose-related decreases in the number of rats engaging in copulatory activity, with 3 mg/kg effecting a virtual elimination in both age groups. In mating tests initiated 60 minutes after treatment, no decrease in the number of rats engaging in copulatory activity was seen in the young animals, and 3 mg/kg caused only a minor reduction in the number of middle-aged males achieving ejaculation.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of apomorphine and haloperidol on plasma cortisol levels in conscious dogs

Cortisol levels were measured in peripheral plasma of conscious dogs after i. v. administration of apomorphine, a dopaminergic agonist, haloperidol, a dopaminergic antagonist, or apomorphine in combination with haloperidol. Apomorphine in a dose of 0.001 and 0.005 mg/kg did not cause any release of cortisol whereas 0.01 and 0.05 mg/kg caused a dose dependent and peakshaped increase of plasma cortisol levels from 20 to 30 and from 20 to 60 ng/ml respectively. Basal levels were reached again within 1 h. Haloperidol (0.1 mg/kg), when given alone, induced a continuous rise of plasma cortisol levels. After 60 min the levels were ?80 ng/ml and still tended to rise. Jf apomorphine (0.01 mg/kg) was given 30 min after the injection of haloperidol (0.1 mg/kg) no further effect of the apomorphine injections was observed. We therefore speculate that apomorphine activates central dopaminergic receptors which cause a release of ACTH from the pituitary into the circulation, which in turn stimulates the release of cortisol from the adrenals. The fact that not only apomorphine but also haloperidol stimulated cortisol release suggests a complex role of dopamine transmission involving different dopaminergic pathways as well as different dopamine receptors. It is also possible that injection of haloperidol induces a stress reaction in the dogs, which causes a release of cortisol from the adrenals.     

Passive avoidance learning in young chicks: Time of day effects

Day old chicks hatched from 17±1 day old fertilised eggs under a 14:10 L/D cycle (lights on:0700 hr; lights off:2100 hr) were trained at 0800, 1200, 1600 and 2000 hr on day 1 posthatch on a single trial passive discriminated avoidance task and tested for retention 24 hr later. Chicks trained at 0800, 1200 and 1600 hr showed evidence of learning but differed in the nature of what was remembered. Discrimination memory is best when training took place at 1200 hr but poorest at 1600 hr, when chicks tended to generalise avoidance to a previously non-aversive stimulus. Chicks trained at 0800 hr showed as much discrimination memory as generalised avoidance. At 2000 hr any evidence of avoidance learning was compromised by a naturally high level of avoidance of pecking at this time of day. There was no evidence of systematic variation in locomotor activity during the light period associated with the changes observed in learning and memory. However, control chicks exhibited a high level of pecking activity at 1600 hr relative to the other times. The findings support the possibility that learning of and memory for a single trial passive discriminated avoidance task may be affected by time of day of training. It is suggested that the results may be due to a complex interaction of arousal, pecking activity and time of day.     

The effects of apomorphine and haloperidol on memory consolidation in the day-old chick

Apomorphine was found to disrupt memory consolidation in a dose-dependent manner on chicks trained on a 1-trial passive avoidance task with a strong aversant experience. Chicks injected with 4.0 mg/kg apomorphine displayed memory deficits at 180 min after learning and showed marked behavioral disturbances, including increased locomotion and increased pecking at the feet of conspecifics. Pretreatment with the dopamine antagonist haloperidol eliminated the memory disturbance induced by apomorphine and facilitated consolidation of memory in chicks given a weak (20% vol/vol methyl anthralinate) training experience. Time-of-retention data suggested that the memory disruption occurred from 120 min after learning, leading to the suggestion that dopamine-related modulation of the training experience may be involved in late-memory formation processes.     

Effects of haloperidol on the acquisition of a spatial learning task.

The effects of systemic injections of the dopaminergic antagonist haloperidol on the acquisition of the Morris water maze with either a visible or an invisible platform (nonspatial vs. spatial learning) were investigated. An open field test was used for selecting a dosage (< or = 0.1 mg/kg), that (hardly) affected locomotor behaviour. Differential effects were found. At 0.1 mg/kg, haloperidol reduced locomotion in the open field, impaired acquisition in the Morris maze with a visible platform, and blocked escape onto an invisible one. Even though 0.07 mg/kg haloperidol reduced locomotion, both 0.04 and 0.07 mg/kg only impaired Morris maze performance in the spatial version. A large effect was found in the first trial of every day's training block. These results indicate that haloperidol at low doses can lead to a moderate but significant impairment of spatial learning. It is suggested that the effects found are related to the function of the striatal areas in cue- and noncue-directed behaviour.     

Natural haemagglutinins and immune responsiveness in young chicks

Titres of natural haemagglutinins to sheep erythrocytes and of experimentally induced antibodies to Newcastle disease virus (NDV), bovine serum albumin (BSA) and human gammaglobulin (HgG) were determined in White Rock broiler chicks immunised at 28 days of age. There was no relationship between levels of natural haemagglutinins and induced antibody levels or between titres of antibody to NDV and titres of antibody to BSA or HgG. A highly significant correlation (r=0.37) was found between titres of antibody to BSA and to HgG.     

Effects of differential rearing condition on heart rate conditioning and response suppression.

Rats were reared in either an enriched or isolated environment for 60 days following weaning. Neither rearing environment nor sex affected heart rate conditioning. However, when the CS used during conditioning was subsequently presented in a drinking situation, males reared in isolation showed a greater degree of response suppression than did similarly reared females. Males and females reared in the enriched environment did not differ in degree of response suppression.     

Effects of germ-free environment, bursectomy and irradiation on the production of natural and immune opsonins in young chicks

The opsonins for goat erythrocytes present in the circulation of normal chicks after the decline of maternal antibody may be natural antibodies. Natural antibodies for goat erythrocytes are detectable in normal chick serum from 7 days of age. However, various immunosuppressive treatments in earlier life failed to depress the level of opsonins for goat erythrocytes during the first 2 weeks of age. A germ-free environment did not affect phagocytosis. The slower clearance of goat erythrocytes from the circulation of chemically bursectomized or irradiated chicks was in proportion to the degree of runting. Weight-adjusted doses of goat cells given to such runted chicks were cleared at the same rate as larger doses in control birds. No specific suppression of opsonin level occurred in the absence of runting. Although the production of immune antibody was depressed by bursectomy in older chicks or by irradiation of 19-day-old embryos immunized in mid-embryonic life, there was no such inhibition of the production of natural opsonins.     

长期甲醛暴露对幼年小鼠学习记忆能力的影响

目的:研究长期甲醛暴露对幼年小鼠学习记忆能力的影响及分子机制。方法:将72只幼年C57BL/6小鼠分为对照组(control)、低浓度甲醛暴露组(FA-L)、中浓度甲醛暴露组(FA-M)和高浓度甲醛暴露组(FAH)。小鼠进行为期30 d不同浓度的甲醛暴露,称量小鼠体重变化,然后通过Morris水迷宫实验检测各组小鼠学习记忆能力,利用Nissl染色观察小鼠海马神经元结构变化,利用商品化试剂盒检测海马组织中超氧化物歧化酶(SOD)活性和丙二醛(MDA)含量,利用Western Blot检测active caspase-3和Bcl-2等分子的表达变化。结果:与对照组小鼠相比,甲醛暴露小鼠体重增长缓慢,学习记忆能力下降,海马神经元数量减少,海马组织中SOD活性下降,MDA生成增加,active caspase-3水平增加,同时Bcl-2表达下降。结论:长期甲醛暴露可导致小鼠学习记忆能力下降,其作用机制与氧化应激反应增加并导致海马细胞凋亡有关。     

Enhanced suppression of a conditioned avoidance response by haloperidol but not phenoxybenzamine in rats with bilateral parafascicular lesions

Summary Male rats were subject to bilateral lesions in the parafascicular nucleus (PF) of the thalamus. The lesions had little or no effect on the performance of a pre-operatively acquired conditioned avoidance response. However, the PF lesioned animals displayed an enhanced response to the dopamine receptor blocking agents haloperidol or pimozide but not to the noradrenaline receptor blocking agent phenoxybenzamine. The results indicate that intralaminar thalamic nuclei and dopaminergic extrapyramidal motor pathways are functionally connected.     

Estrogen-induced changes in place and response learning in young adult female rats

Many findings suggest that changes in circulating estrogen levels influence cognition, in some cases impairing performance and in others enhancing performance. One interpretation of these mixed effects is that estrogen biases the strategy used to solve a task. To test this idea, young adult female rats, ovariectomized for 21 days, were trained after acute hormone or control treatment in 2 very similar tasks with different cognitive requirements. One task required place learning and the other response learning. Rats given two 10-microg injections of estradiol 48 and 24 hr before training learned the place task significantly faster than did rats without estradiol. Conversely, rats without estradiol performed better on the response task than did rats with replacement. These data suggest that the cognitive actions of estrogen may be task-specific by modulating the relative contribution of different learning and memory systems.     

Effects of the dopamine antagonists haloperidol and domperidone on the normoxic ventilatory response to CO2 in cats

We investigated the effects of the dopamine antagonists haloperidol and domperidone on the ventilatory response following square-wave changes in end-tidal CO₂ during normoxia in chloralose-urethane anaesthetized cats. In 7 cats these responses were measured before (control, 28 runs) and after the administration of 1 mg/kg haloperidol i.v. (26 runs) and in 8 other cats before (39 runs) and after 0.5 mg/kg domperidone i.v. (34 runs). Each response was separated into a slow central and a fast peripheral part by fitting two exponential functions to the measured ventilation. These functions have as parameters a CO₂ sensitivity, a time constant, a time delay and an apnoeic threshold B (extrapolated PETCO₂ of the steady-state response curve at zero ventilation). Haloperidol significantly diminished the peripheral (Sp) and the central (Sc) ventilatory sensitivity to CO₂ and the B-value (P<0.001). The ratio Sp/Sc, the time constants and the time delays were not significantly changed. Domperidone only diminished the B-value significantly (P<0.001). Since domperidone does not readily cross the blood-brain barrier, its effect was a CO₂ independent increase of the ventilation mediated by the peripheral chemoreceptors. Haloperidol exhibited, besides the peripheral stimulatory effect a depressant central effect due to an action on the central integrative structure, resulting in a proportional decrease of Sp and Sc.     

The effect of cold stress on muscle growth in young chicks.

The effect of cold stress on muscle growth in young poultry stock has been examined during an experiment involving one hundred and eight chicks. They were divided into two groups, namely the control group and the cold stress group. The newly-hatched chicks of broiler type were chilled at a temperature of 10 degrees C for a total of four hours. The breast and thigh muscles of one side of each bird were analyzed for fat, protein, potassium, magnesium, calcium, and sodium during the two weeks after hatching. In the stressed chicks, body weight, breast and thigh muscle weight were consistently lower over the fortnight than in the controls. The body weight of the stressed birds was increased by two-fold, whereas, in the controls, the increase was there and a half times. The breast and thigh muscle weights of the stressed chicks increased by seven times and two times, respectively. In the normal birds breast and thigh muscle weights were enhanced fifteen times and four times, respectively. The protein content of the breast muscle in the normal birds was enhanced by thirty-fold and that of the thigh muscle by five-fold. In the stressed chicks the increase in the protein content in the breast muscle was twelve-fold and that of the thigh muscle was two-fold. Muscle fat content was lower in the chilled birds than in the controls. Levels of potassium and magnesium were also lower in the stressed chicks than in the normal birds.     

Effects of apomorphine on rat behavior in the elevated plus-maze

It has been reported that novelty may evoke both an exploratory and a fear drive, thus generating behavior responding to an approach/avoidance conflict. However, not much is known about the approach component. Whereas there exists abundant evidence referring to the avoidance component as the main target for the anxiolytic action of benzodiazepines, the involvement of dopaminergic mechanisms in fear and anxiety is controversial. The present study examined the effects of the dopaminergic agonist apomorphine, the D₂ dopaminergic antagonist sulpiride and the combined treatment sulpiride plus apomorphine on conventional and non-conventional measures of the behavior of rats exposed to an elevated plus-maze. Systemic injection of apomorphine (0.25, 0.5 and 1.0 mg/kg) caused a selective increase in the time spent in the open arms and in the open arm extremities. Pre-treatment with sulpiride blocked these effects while this dopaminergic antagonist had no effect by its own. Apomorphine produced no significant effects on stretching, flat-back-approach or scanning. Therefore, apomorphine increased the behavioral response linked to the approach component of the conflict without affecting risk assessment behaviors. These findings suggest that dopaminergic mechanisms, probably through D₂ receptors, may also be involved in the mediation of the conflict derived from the need of gathering information for confirming, identifying and localizing danger and take the appropriate action for avoiding the threatening stimuli of the elevated plus-maze. A role for dopaminergic mechanisms in the setting up of adaptive responses in a fear-inducing environment is discussed.     

Color preferences and early perceptual discrimination learning in domestic chicks

The speed of learning to discriminate between the colors blue and green was studied in dark-raised chicks and in chicks having controlled exposure to these colors and white prior to learning. The data indicate that: (1) under all conditions of prior experience learning was faster when the response to blue was reinforced; (2) learning was significantly slower in dark-raised groups than in groups having prior visual experience; and (3) learning was negatively related to systematic increase in the intensity of prior exposure stimulus. These data show that unlearned preferences play a significant role in learning; they combine additively with effects of experience prior to learning and reinforcement during learning.     

Effects of lateral, medial, or complete septal lesions on response suppression.

Two groups of rats were fed 2 different diets—a high-dextrose (D) diet and a high-fat (F) diet for 20 days. Intravenous glucose tolerance tests (IVGTT) were performed, and 5 days later, effects of a single 6 μg dose of estradiol benzoate (EB) upon daily food intake were assessed. F-fed rats were more intolerant to glucose than D-fed rats, and also responded to EB with greater decreases in feeding. Levels of plasma glucose at t=60 min during the IVGTT were significantly correlated (p<0.01) with subsequent maximal responses to EB for F-fed rats. It was proposed that impairment of glucose tolerance leads to increased responsiveness to anorexic effects of EB, perhaps via an altered glucose metabolism of the ventromedial hypothalamus, a site of action of estrogen.