Behavior of rats during chronic activation and blockade of the neostriatal opiate system

The effects of daily microinjections (MI), over the course of three weeks, bilaterally into the rostral striatum, of morphine, promedol, native leu-enkephalin and its synthetic tetrapeptide analogs were studied in experiments on rats. Naloxone was used as an antagonist. An active avoidance conditioned reflex was developed preliminarily in a shuttle box. A decrease in the accuracy of the realization and an increase in the latent period of the reflex were observed after the first MI of morphine and enkephalins. The effect in the most stable aminated ornithine-containing tetrapeptides proved to be the strongest. A search stereotypy and increased motoric activity were recorded in the rats during the development of the chronic effects of the activators of the opiate system. A clear correlation was not found between the motor and conditioned reflex shifts. The blockade of the opiate receptors with naloxone did not lead to substantial changes in behavior. The data obtained confirm the current hypothesis regarding the important role of the enkephalinergic system of the neostriatum in the regulation of complex forms of behavior and its close functional association with the dopaminergic system. I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, Saint Petersburg. Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 44, No. 2, pp. 283–290, March–April, 1994.     

Activation of neostriatal dopaminergic system in rats prevents toxic effects of picrotoxin administered into globus pallidus

Multiple bilateral microinjections of 5 μg picrotoxin (antagonist of chloride channels coupled with GABA_A receptors) into the globus pallidus induced lethal seizures in some rats and impaired conditioned avoidance responses in survivors. Administration of 15 μg amphetamine into the rostral neostriatum prevented picrotoxin-induced lethal seizures and reduced its negative effects on active avoidance behavior. Activation of the neostriatal dopaminergic system in animals receiving no intrapallidal picrotoxin promoted recovery of conditioned responses after implantation procedure. Translated fromByulleten' Eksperimental'noi Biologii i Meditsiny, Vol. 130, No. 8, 144–146, August, 2000     

Activation of neostriatal dopaminergic system in rats prevents toxic effects of picrotoxin administered into globus pallidus

Multiple bilateral microinjections of 5μg picrotoxin (antagonist of chloride channels coupled with GABA_A receptors) into the globus pallidus induced lethal seizures in some rats and impaired conditioned avoidance responses in survivors. Administration of 15 μg amphetamine into the rostral neostriatum prevented picrotoxin-induced lethal seizures and reduced its negative effects on active avoidance behavior. Activation of the neostriatal dopaminergic system in animals receiving no intrapallidal picrotoxin promoted recovery of conditioned responses after implantation procedure. Translated fromByulleten’ Eksperimental’noi Biologii i Meditsiny, Vol. 130, No. 8, 144–146, August, 2000     

The influence of chronic activation and blockade of the dopamine- and enkephalinergic systems of the neostriatum on conditioned reflex behavior and dopamine metabolism in the rat nigrostriatal system

The effects of daily injections, over the course of 14 days, of 45 g of phenamine, 5 g of haloperidol and naloxone, 15 g of leuenkephalin and its analog, a tetrapeptide, into the rostral neostriatum have been studied. The chronic stimulation of the dopaminergic system of the striatum induced facilitation of the realization of an active avoidance conditioned reflex, and stimulated exploratory stereotypy, while its blockade led to suppression of conditioned reflex activity against the background of a clearcut rigid akinetic syndrome. The microinjections of leu-enkephalin and naloxone did not substantially alter the behavior, but the injection of the tetrapeptide was accompanied by changes in behavior, with symptoms of catalepsy and hyperkinesia. Injections of phenamine and haloperidol were accompanied by a decrease in the content of dopamine in the striatum and an increase in the level of DOPAC; the injections of enkephalin and naloxone induced changes of the reverse order. The possible causes of the noncorrespondence of the behavioral and neurochemical shifts in the presence of a direct chronic pharmacological action on the mediator of the neostriatum.Translated from Zhurnal Vysshei Nervnoi Deyatel'nosti imeni I. P. Pavlova, Vol. 42, No. 5, pp. 930–935, September–October, 1992.     

慢性间歇性低压低氧对老年大鼠自发运动行为及黑质多巴胺能神经元的影响

目的:用慢性间歇性低压低氧(CIHH)模型,探讨CIHH对老年大鼠自发运动行为以及黑质多巴胺能神经元的影响。方法:用CIHH模型处理老年大鼠30 d,通过旷场实验检测大鼠自发运动行为的改变,通过实时定量PCR和免疫印迹检测黑质多巴胺能神经元酪氨酸羟化酶(TH)和多巴胺转运体(DAT)表达的变化。结果:老年组大鼠旷场实验中闻嗅行为、探索行为、运动行为和理毛行为与成年组相比均显著下降,CIHH处理后理毛行为没有改变,闻嗅行为、探索行为和运动行为显著改善,但没有达到成年组水平;老年组大鼠黑质多巴胺能神经元TH和DAT的表达与成年组相比均显著下降,老年CIHH组TH和DAT的表达升高,但没有达到成年组水平。结论:CIHH可改善老年大鼠闻嗅行为、探索行为和运动行为,并提高黑质多巴胺能神经元TH和DAT的表达。     

The possible participation of a dopaminergic system in mutilating behavior in rats with forelimb deafferentation

The role of sodium (Na) in stimulus-secretion coupling of adrenal medulla was investigated in primary culture of bovine adrenal medulla cells. In Na-free medium, the secretion of catecholamines and influx of 45Ca induced by carbachol were decreased to 30% and 18% of control responses, respectively. Carbachol induced secretion of catecholamines and influx of 45Ca were not inhibited by tetrodotoxin, a highly selective blocker of voltage dependent Na-channels. Carbachol caused a rapid influx of 22Na which was inhibited by hexamethonium but not by tetrodotoxin. Nicotine but not muscarine could be a substitute for carbachol and caused catecholamine secretion, 45Ca influx 22Na influx. Veratridine caused continuous secretion of catecholamines and influxes of 45Ca and 22Na which were blocked by tetrodotoxin. These results indicate that in cultured bovine adrenal medulla cells, stimulation of nicotinic receptor causes the influx of Na through receptor-mediated Na-channels but not through voltage-dependent Na-channels, and that influxed Na may facilitate the influx of Ca which triggers the secretory process. The sodium ion seems to be involved in the stimulus-secretion coupling evoked by physiological secretagogue in adrenal medulla.     

Structural characteristics of renal glomerular system in ISIAH rats under conditions of chronic stress and preventive hypotensive drug therapy

The effects of chronic stress on the structure and function of the renal glomerular system were studied in hypertensive ISIAH rats treated with hypotensive drugs during the early ontogeny. The morphometric parameters of the renal glomerular system, characteristic of each of the experimental animal groups treated by enalapril, losartan, or terazosin in early age virtually did not change under conditions of stress exposure. These results indicate a persistent delayed nephroprotective effect of these drugs.     

Cytochemical manifestations of short- and long-term activation of the rat brain dopaminergic system

Laboratory of Cytochemistry, Brain Research Institute, Academy of Medical Sciences of the USSR, Moscow. (Presented by Academician of the Academy of Medical Sciences of the USSR O. S. Adrianov.) Translated from Byulleten' Éksperimental'noi Biologii i Meditsiny, Vol. 112, No. 7, pp. 41–42, July, 1991.     

Effects of postweaning undernutrition on exploratory behavior, memory and sensory reactivity in rats: implication of the dopaminergic system

The effects of early undernutrition on behavior and brain biochemistry were examined in rats. At weaning, rats were provided either an ad lib diet (control group) or maintained at 80% of the weight of their control littermates (undernourished group). Three weeks into the diet they were tested in an open field. After 6 weeks of diet, HPLC analyses were conducted on sample brains from each group to assess levels of dopamine and metabolites, respectively dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) in the striatum. At seven weeks of diet, remaining rats were trained in an 8-arm radial maze, and a retention test conducted 72 h after attaining the learning criterion. At fourteen weeks of diet, sensory reactivity was measured by tail-immersion in a water bath maintained at constant temperature 50 +/- 1 degrees C. Undernourished rats exhibited hyperactivity and increased exploratory behavior in the open field, as well as increased sensory reactivity in the tail flick test. In the radial maze, however, undernourished rats did not differ from controls in either learning or retention. Haloperidol (i. p. injection) impaired retention by control but not undernourished animals. HPLC analyses showed an increase in dopamine turnover in the striatum of undernourished rats. Our results suggest that, unlike its effects when induced immediately at birth or in adulthood, undernutrition at weaning does not appear to influence learning and retention but induced an hyperactivity and alterations in striatal DA turnover which was associated with a decrease in responsiveness to i. p. haloperidol injection.     

Correlations of motility, defecatory behavior and striatal dopaminergic activity in rats

The spontaneous motor activity, fecal pellet scores and content of dopamine and its metabolites, dihydroxyphenyl acetic acid and homovanillic acid in corpus striatum were measured in a group of randomly selected Sprague-Dawley rats. The spontaneous motility, fecal pellet scores and neurochemical parameters measured showed significant variations. The correlations between these parameters were investigated. A significant correspondence was seen between the motility, fecal pellet scores and the striatal dopaminergic activity. The implications of the behavioral models of motility and defecation scores in studying the central dopaminergic function is discussed. It is suggested that striatal dopaminergic activity may be responsible not only for motor activity but also may contribute to the de novo emotionality as expressed by the defecation scores in rats.     

Plasma cortisol activity in rats under conditions of chronic stress supplemented with resveratrol

Objective:

To determine the activity of cortisol in rats treated with exogenous adrenocorticotropic hormone (ACTH) and a resveratrol supplement.

Methods:

Forty-eight adult female rats and 16 male rats of the strain (Rattus norvegicus) that were three months old and with body weights ranging from 200 to 250 g for females and 300 to 350 g for males were used and kept in controlled environmental conditions: temperature of 20±2° C and light-dark cycles of 14 and 10 hours. They were fed a balanced diet and had free access to water. The rats were randomly divided into four groups: group 1 - was treated with 5 µg/kg of ACTH i.p. every twelve hours; group 2 - received the same treatment with ACTH plus a grape extract supplement (resveratrol) of 40 mg/kg; group 3 - only received grape extract (resveratrol); and group 4 - received a saline solution (0.9%) i.p. and oral, and served as controls. The experimental design was a 2×2 factorial with two levels ACTH and two polyphenol levels (grape extract).

Results:

No significant differences were found in blood cortisol concentrations, by day and gender, or by treatment effects (0.75 µg/dL ± 0.11; p <0.001).

Conclusion:

Results suggest that chronic stress and consumption of resveratrol did not directly alter levels of plasmatic cortisol in either stressed or unstressed rats. It was concluded that the given dosage levels of ACTH possibly did not produce sufficient stimulation of the adrenal gland for these animals.     

The development of sexual behavior in anosmic male rats reared under various social conditions

Male rats were made anosmic when 30 days old and reared either together with female littermates or isolated. The rats were tested for sexual behavior when 95 days old. The anosmic peer-deprived rats showed a total suppression of sexual behavior. A few of the group-reared anosmic males mounted the female in the first test. At the end of testing 50% were still sexually inactive. Compared with the intact group-reared rats, the anosmic group-reared rats showed an increased number of mounts preceding ejaculation and prolonged response latencies. Eighty-five percent of the peer-deprived rats showed complete sexual behavior during the course of testing while 70 percent of the group-reared males mounted and ejaculated already in the first test and 90 percent were sexually active at the end of testing. When mating, the intact peer-deprived rats showed an impaired mating pattern compared to the intact group-reared rats, involving an increased number of mounts and intromissions preceding ejaculation and prolonged intromission — and ejaculation latencies. This impairment still persisted at the end of testing.     

Cardiotropic effects of met-enkephalin and somatostatin under conditions of neurotensin receptor blockade

Pretreatment with the neurotensin receptor antagonist decreased the severity and time of Met-enkephalin-induced inhibition of vagal chronotropic effects in cats. The opiate receptor antagonist naloxone produced a delayed inhibitory effect on the synchronizing component of the vagal chronotropic effect under conditions of neurotensin receptor blockade. Cardiotropic effects of somatostatin remained unchanged during neurotensin receptor blockade. These data indicate one-way and two-way interactions between peptides modulating parasympathetic cardiac regulation.     

Cardiotropic effects of met-enkephalin and somatostatin under conditions of neurotensin receptor blockade

Pretreatment with the neurotensin receptor antagonist decreased the severity and time of Metenkephalin-induced inhibition of vagal chronotropic effects in cats. The opiate receptor antagonist naloxone produced a delayed inhibitory effect on the synchronizing component of the vagal chronotropic effect under conditions of neurotensin receptor blockade. Cardiotropic effects of somatostatin remained unchanged during neurotensin receptor blockade. These data indicate one-way and two-way interactions between peptides modulating parasympathetic cardiac regulation.     

Guidance of instrumental behavior under reversal conditions requires dopamine D1 and D2 receptor activation in the orbitofrontal cortex

The orbitofrontal cortex (OFC) plays a critical role in learning a reversal of stimulus-reward contingencies. Dopamine (DA) neurons probably support reversal learning by emitting prediction error signals that indicate the discrepancy between the actually received reward and its prediction. However, the role of DA receptor-mediated signaling in the OFC to adapt behavior to changing stimulus-reward contingencies is largely unknown. Here we examined the effects of a selective D1 or D2 receptor blockade in the OFC on learning a reversal of previously acquired stimulus-reward magnitude contingencies. Rats were trained on a reaction time (RT) task demanding conditioned lever release with discriminative visual stimuli signaling in advance the upcoming reward magnitude (one or five food pellets). After acquisition, RTs were guided by stimulus-associated reward magnitudes, i.e. RTs of responses were significantly shorter for expected high versus low reward. Thereafter, stimulus-reward magnitude contingencies were reversed and learning was tested under reversal conditions for three blocks after pre-trial infusions of the selective D1 or D2 receptor antagonists R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepinhydrochloride (SCH23390), eticlopride, or vehicle. For comparisons, we included intra-OFC infusions of the selective N-methyl-d-aspartate receptor antagonist AP5. Results revealed that in animals subjected to intra-OFC infusions of SCH23390 or eticlopride learning a reversal of previously acquired stimulus reward-magnitude contingencies was impaired. Thus, in a visual discrimination task as used here, D1 and D2 receptor-mediated signaling in the OFC seems to be necessary to update the reward-predictive significance of stimuli.     

Influence of the mesocortical dopaminergic system on activity, food hoarding, social-agonistic behavior, and spatial delayed alternation in male rats

In order to assess the behavioral role of the dopaminergic mesocortical input to the prefrontal cortex, bilateral lesions were made in the ventral tegmental area (VTA). The possibility of a functional recovery by the administration of a dopamine agonist was examined. General activity, food hoarding, social-agonistic behavior, and spatial delayed alternation performance were recorded in rats with VTA lesions and in sham-operated animals. In the open field animals with VTA lesions were more active but showed less anxiety. Food hoarding was impaired. In dyadic interactions with sham-operated opponents, VTA rats were socially more active, whereas sham operates performed more keeping down and aggressive grooming. This behavioral deficit was partially recovered when apomorphine was administered prior to testing. VTA animals were impaired in the performance of a spatial delayed alternation task with an intertrial interval of 15 s, whereas no impairment was found with a 0-s intertrial interval. The theoretical implications of these findings are discussed.