Repeated isolation in the neonatal rat produces alterations in behavior and ventral striatal dopamine release in the juvenile after amphetamine challenge.

Rat pups were isolated from the mother and nest for 1 hr per day from Postnatal Day (PN) 2 to 9. At PN 27, rats were tested for behavioral responsiveness to 2.0 or 7.5 mg/kg amphetamine. Only isolated rats receiving the 7.5 mg/kg dose displayed increased activity scores, compared with nonisolated and nonhandled controls. Their increased activity is attributed to a slower latency to enter into stereotypy. In a second experiment, similarly treated groups were challenged by the 7.5 mg/kg dose during a session in which a microdialysis probe implanted in the ventral striatum was being perfused. The challenge drug elicited a much greater increase in dialysate dopamine in isolated vs nonisolated groups. Results are discussed with regard to dissociation between sensitized and subsensitized responses. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of isolation conditions on brain regional enkephalin and !b-endorphin levels and vocalizations in 10-day-old rat pups.

Young rat pups were isolated from their dams under different conditions. The endogenous opioid peptides were measured in brain regions after isolation. Because there is no uptake mechanism for peptides released at the synapse and because released peptide is rapidly degraded enzymatically, decreases in peptide levels over this time course can be interpreted as release from terminals. No change was observed in either peptide in the hypothalamus, septum, or amygdala after isolation compared with controls. Significant decreases were seen in the midbrain after isolation. A comparison of peptide levels and ultrasonic vocalizations in the pups isolated in familiar, novel, or control conditions was also performed. Enkephalin levels in the midbrain were decreased in familiar and novel conditions, but in the brainstem opioid peptides were decreased only in the familiar condition. The greater involvement of the opioid peptides in the pups isolated in familiar conditions may contribute to the ability of naltrexone to block vocalization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cocaine-induced effects on isolation stress in neonatal rats.

The effects of cocaine administration on isolation-induced vocalizations and activity levels in 10-day-old rat pups were examined. Day 10 pups given cocaine (1.25, 2.5, 5, 10, and 20 mg/kg ip) vocalized significantly less than their caffeine- (10 mg/kg) and saline-administered siblings during a 5-min isolation period. Cocaine- and caffeine-administered pups also demonstrated a significant increase in overall activity compared with controls. In addition, ip administration of the dopamine antagonist haloperidol (0.5 and 1.0 mg/kg) before 1.25 and 2.5 mg/kg cocaine produced a significant elevation in vocalizations compared with saline pretreatment, which indicates a blocking of cocaine's effect on calling behavior. These results suggest that the endogenous dopamine system involved with reinforcement and reward may quell the stress of isolation in the infant rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Self-stimulation in 7- and 10-day-old rats.

It has been shown that the infant rat exhibits learned behaviors characteristic of the adult. With a modified self-stimulation paradigm, the present study explored whether 7- and 10-day-old Long-Evans rat pups could learn a discriminated operant to obtain direct electrical stimulation in neural sites that support self-stimulation in adults. By nudging 1 of 2 response manipulanda, at 2 ages (7 and 10 days) and temperatures (22 and 35°C), Ss self-stimulated with electrodes implanted in a variety of forebrain sites, including the prefrontal cortex, bed nucleus of the stria terminalis, medial nucleus of the amygdala, and the medial forebrain bundle. The only temperature-sensitive site might be the nucleus accumbens, which was positive only at the higher temperature in 10-day-olds. Results indicate that several forebrain sites demonstrate rewarding properties of stimulation in the preweanling rat pup. (40 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of neonatal dopamine depletion on sensory inhibition in the rat

Central dopamine systems appear to play an important role in sensory information processing. In particular, the filtering (or gating) of repetitive auditory stimuli is modulated by pharmacological manipulations that affect dopaminergic neurotransmission. The present study further addressed the role of dopamine in auditory gating. Three-day-old male Sprague-Dawley rats, pretreated with desipramine, received intracisternal injections of 6-hydroxydopamine (6-OHDA; 75 micrograms in 10 microliters) or the vehicle. At 4 months of age the rats were implanted for evoked potential recording and auditory gating was assessed using a paired click paradigm. Neonatally administered 6-OHDA did not alter gating in the adult rats. However, unlike for the control group, systemic amphetamine (1.83 mg/kg, IP) failed to disrupt gating in the treated rats. Apomorphine (1.0 mg/kg, SC) disrupted gating in both groups. Neonatal 6-OHDA treatment caused significant reductions in dopamine levels in the striatum, nucleus accumbens, and substantia nigra/ventral tegmental regions. There was an inverse relationship between substantia nigra/ ventral tegmental area dopamine levels and auditory gating. Overall, the results suggest that amphetamine-induced auditory gating loss requires presynaptic dopamine release, but that the deficiency occurs through postsynaptic dopamine receptor activation.     

Effects of prenatal gamma-irradiation on the astrocyte proliferation in response to injury in the brain of 6-day-old rat

Pregnant Wistar rats were exposed to a single 1.0 Gy dose of gamma rays on gestational days 13, 15, 17 or 19 (E13, E15, E17 and E19, respectively). A mechanical injury was made in the cerebral hemisphere of their 6 day-old male offsprings. The injured rats were injected with [3H]thymidine on day 1 or 2 after injury and killed 4 h after the injection. Brain sections were immunostained for glial fibrillary acidic protein (GFAP) or S-100beta protein, subjected to autoradiography and examined microscopically to record proliferating astrocytes. The intensity of astrocyte proliferation in response to injury showed a gradual decrease from the level maximal in brains irradiated on E13 to minimal in those irradiated on E19. The changes were regarded as being related to the stage of prenatal development when irradiation of the brain was performed.     

Interleukin-1 beta stimulates adrenocorticotropin and corticosterone release in 10-day-old rat pups

Clinical, radiological and biological features of 19 cases of serologically proven Mycoplasma pneumoniae pneumonia were compared with those of 21 cases of other types of pneumonia. Some clinical features were more frequent in M pneumoniae: patients older than 5 years, association with upper respiratory tract infection, skin rashes, acute course, unsuccessful treatment with penicillin. There were no specific radiological features. When compared with the complement fixation method, the serological diagnosis using agglutination technique appears to be more sensitive.     

Endogenous cholecystokinin reduces vocalization in isolated 10-day-old rats.

Devazepide, the cholecystokinin (CCK) receptor blocker, markedly and specifically affected the behavior of 10-day-old rats isolated from mother and siblings. Whereas intraoral infusions of milk or fat, which cause CCK release, calmed infants, that is, reduced levels of ultrasonic vocalization, devazepide fully blocked this reduction. Devazepide did not reduce the elevated pain limen caused by milk or fat infusions. These data parallel earlier findings obtained with administration of exogenous CCK and implicate endogenous CCK in the maintenance of infant steady state and calm. The possibility that CCK contributes to the normal development of mother–infant affectional systems is discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Opioidlike effects of intraoral infusions of corn oil and polycose on stress reactions in 10-day-old rats.

The effects of intraoral infusions of corn oil and the polysaccharide Polycose on behavioral reactions to pain and to social isolation were studied in 10-day-old albino rat pups. Both substances significantly increased paw-lift latencies (a measure of pain response) and reduced the number of ultrasonic vocalizations (a measure of isolation distress). Moreover, elevated pain thresholds were normalized by naltrexone (0.25 mg/kg) pretreatment, and the quieting of vocalizations was abolished by pretreatment. These findings indicate an interaction between ingestion, pain, and distress systems in neonatal rats and suggest that fats and polysaccharides influence these systems via endogenous opioids. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Regional changes in dopamine and serotonin activation with various intensity of physical and psychological stress in the rat brain

The present study examined whether regional patterns of brain dopamine (DA) and serotonin (5-HT) activation after physical and psychological stress depend on the intensity of that stress. Monoamine concentrations (DA, 5-HT, and their metabolites) were measured using high-performance liquid chromatography with electrochemical detection in eight brain regions of rats exposed to two different intensities of foot shock stress for 30 min (1.5 mA or 2.5 mA) or conditioned fear stress (CFS, after single or repeated foot shock). A low level of foot shock selectively increased the DA metabolism in the medial prefrontal cortex (mPFC), whereas a high level of foot shock increased it in most of the brain regions examined in the present study. A low level of foot shock did not increase the 5-HT metabolism in any regions, but a high-intensity shock increased the 5-HT metabolism in the mPFC, nucleus accumbens, and lateral hypothalamus. Rats that received high-intensity shock displayed more freezing than those that received low-intensity shock in a conditioned fear paradigm (24 h after receiving foot shock, the animals were placed in a shock chamber without being given shock), indicating an augmentation of conditioned fear. The increased DA and 5-HT metabolism were especially marked in the mPFC after CFS following a single foot shock session (2.5 mA). Rats that were repeatedly exposed to 2.5 mA foot shock for a period of 10 days displayed a greater degree of freezing induced by CFS than those given only one foot shock session, indicating an augmentation of fear and stress intensity. CFS after repeated foot shock, like foot shock per se, increased the DA metabolism in most of the brain regions except for the striatum and increased the 5-HT metabolism in the mPFC, nucleus accumbens, and amygdala. These results suggest that regional patterns of brain DA and 5-HT activation after physical and psychological stress depend on the intensity of that stress, although there are some differences between these stress; and that the more widespread activation of DA and 5-HT after more severe stress might relate to behavioral changes that reflect the augmentation of fear.     

Intracerebral injection of interferon-gamma inhibits the astrocyte proliferation following the brain injury in the 6-day-old rat

The present study examines the influence of interferon-gamma (IFN-gamma) on the astrocyte proliferation in the rat brain injured within the early period of postnatal development. Six-day-old male rats received a lesion in the left cerebral hemisphere and a single injection of recombinant rat IFN-gamma into the lesion cavity. One or 2 days after the injury the rats were injected with 3H-thymidine. Brain sections were immunostained for glial fibrillary acidic protein (GFAP), subjected to autoradiography, and examined microscopically to record proliferating GFAP-immunopositive astrocytes labeled with 3H-thymidine. In the IFN-gamma-injected rats, a statistically significant decrease in the intensity of reactive astrocyte proliferation was revealed. On day 1 after injury the intensity of astrocyte proliferation showed dose-dependent changes. Relations between the astrocyte reactivity and multiple factors existing in the injured and IFN-gamma-injected brain are discussed. The results represent the first in vivo evidence of a dose-dependent action of IFN-gamma on the astrocyte proliferation in response to injury.     

Amiloride sensitivity in the neonatal rat.

Amiloride-sensitive sodium (Na) channels in taste buds appear to play a key role in the response to NaCl stimulation, at least in adult rats. The researchers examined whether neonatal rats, which display an exaggerated preference for hypertonic NaCl solutions, lack functional amiloride-sensitive Na channels. NaCl intake was significantly reduced by amiloride pretreatment, but water and ammonium chloride were unaffected. The researchers assessed whether the early appearance of amiloride sensitivity was mediated by effects on chorda tympani (CHT) activity by sectioning the CHT before testing. CHT transection reduced intake of NaCl solutions and eliminated evidence of amiloride sensitivity. Amiloride sensitivity was also assessed by recording of whole-nerve CHT activity at 8 to 11 days of age; the response to NaCl stimulation was significantly suppressed by amiloride. These data indicate that amiloride-sensitive Na channels develop earlier than previously believed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Repeated diazepam administration influences 5-HT1A receptor binding in the rat brain

Repeated administration of diazepam for 14 days (5 mg/kg daily) resulted in a significant increase of 5-HT1A receptor density in the midbrain of the rat. Bmax values were increased from 239.6 to 684.9 fmol/mg. The affinity constants (KD) were also increased, from 0.97 to 3.01 nM/l.     

Dopamine and the structure of personality: Relation of agonist-induced dopamine activity to positive emotionality.

Modern trait theories of personality include a dimension reflecting positive emotionality (PE) based on sensitivity to signals of incentive-reward. In animals, responsivity within an emotional system analog of PE is dependent on brain dopamine (DA) activity. To determine whether human PE trait levels are also associated with central DA, effects of a specific DA D? receptor agonist were assessed in 23 Ss who were widely distributed along the trait dimension of PE. The degree of agonist-induced reactivity in 2 distinct central DA indices was strongly and specifically associated with trait levels of PE, but not with other personality traits. The results suggest that the trait structure of personality may be related to individual differences in brain DA functioning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cardiopulmonary response to dopamine in chronically catheterized neonatal lambs

Seven neonatal lambs were chronically catheterized. An electromagnetic flow probe was placed around the main pulmonary artery, and the ductus arteriosus ligated. After recovery, dopamine's effect was tested at 10 doses over the range 1--400 micrograms/kg/min in 12 studies, at ages 3 to 16 days. Pulmonary vascular resistance (PVR) increased from 0.093 +/- 0.01 to 0.14 +/- 0.02 mm Hg/ml/kg/min at the highest dose. Systemic vascular resistance (SVR) was unchanged at doses less than 20 micrograms/kg/min, but increased 99% from 0.38 +/- 0.04 to 0.79 +/- 0.08 mm Hg/ml/kg/min (P less than 0.005) at 200--400 micrograms/kg/min. The ratio PVR/SVR increased 18% from 0.26 +/- 0.32 to 0.32 +/- 0.05 at a dose of 17--20 mg/kg/min, then declined to 0.19 +/- 0.03 at 200--400 microgram/kg/min (P less than 0.05). Pulmonary blood flow was unchanged. Left atrial pressure increased sharply at doses above 50 micrograms/kg/min (P less than 0.005). Transient bradyarrhythmia occurred in 9 of 12 studies at infusion rates of 50--200 micrograms/kg/min. Heart rate did not change until recovery when it increased (48%) from 181 to 292 (P less than 0.005). These data suggest that the dopamine response in the intact neonate is complex with divergent and dose-dependent effects on the pulmonary and systemic circuit.     

Influence of neonatal and adult hyperthyroidism on behavior and biosynthetic capacity for norepinephrine, dopamine and 5-hydroxytryptamine in rat brain

In neonatal rats, administration of l-triiodothyronine (10 mug/100 g/day) for 30 days presented signs of hyperthyroidism which included accelerated development of a variety of physical and behavioral characteristics accompanying maturation. The spontaneous motor activity was increased by 69%. Exposure of developing rats to thyroid hormone significantly increased the endogenous concentration of striatal tyrosine and the activity of tyrosine hydroxylase as well as the levels of dopamine in several brain regions. The concentration of striatal homovanillic acid and 3,4-dihydroxyphenylacetic acid, the chief metabolites of dopamine, was also increased and the magnitude of change was greater than the rise in dopamine. Despite increases in the activity of tyrosine hydroxylase and the availability of the substrate tyrosine, the steady-state levels of norepinephrine remained unaltered in various regions of brain except in cerebellum. Futhermore, neonatal hyperthyroidism significantly increased the levels of midbrain tryptophan and tryptophan hydroxylase activity but produced no change in 5-hydroxytryptamine levels of several discrete brain regions, except hypothalamus and cerebellum where its concentration was slightly decreased. However, the 5-hydroxyindoleacetic acid levels were enhanced in hypothalamus, ponsmedulla, midbrain, striatum and hippocampus. The elevated levels of 5-hydroxyindoleacetic acid did not seem to be due to increased intraneuronal deamination of 5-hydroxytryptamine since monoamine oxidase activity was not affected in cerebral cortex and midbrain of hyperthyroid rats. The data demonstrate that hyperthyroidism significantly increased the synthesis as well as the utilization of catecholamines and 5-hydroxytryptamine in maturing brain. Since the mature brain is known to respond differently to thyroid hormone action than does the developing brain, the effect of L-triiodothyronine treatment on various putative neurohumors also was examined in adult rats. Whereas administration of l-triiodothyronine (10 mug/100 g/day) for 30 days to 120-day-old rats increased the levels of tyrosine by 23% and of tryptophan by 43%, no appreciable change was noted in tryptophan hydroxylase activity. In contrast to neonatal hyperthyroidism, excess of thyroid hormone in adult rats failed to produce any change in motor activity and tended to decrease striatal tyrosine hydroxylase activity only slightly. The concentration of dopamine remained unchanged in all regions of the brain except in midbrain where it rose by 19%. Whereas norepinephrine concentration was altered in hypothalamus, pons-medulla and midbrain, the levels of 5-hydroxytryptamine and its metabolite, 5-hydroxyindoleacetic acid, were significantly decreased in striatum and cerebellum. Since dopaminergic and noradrenergic neurons are the critical components of the motor system, the possibility exists that elevated behavioral activity in young L-triiodothyronine-treated animals might be associated with increased turnover of catecholamines in neuronal tissue.     

Interactions between contact and chemosensory mechanisms in pain modulation in 10-day-old rats.

Antinociception was evaluated in 10-day-old rats while suckling or in contact with the mother. Testing occurred during, immediately after, or at 30 and 60 sec following milk-induced hyperextension. Hyperextension-induced hypoalgesia terminated immediately with stretch cessation. For suckling rats, baseline escape levels were reachieved within 1 min. For contact rats, baseline levels were also manifest at 30 sec but were elevated by 1 min. Sublingual infusions into the anterior portion of the mouth in rats that were either suckling or in contact caused a 20–25-sec increase in escape latencies. For suckling rats, escape latencies returned to baseline levels immediately at infusion termination. For contact rats, latencies continued to be elevated for at least 5 min postinfusion. Thus, 3 classes of mother–infant interactions, contact, suckling, and hyperextension during milk letdown, cause varying degrees of hypoalgesia in 10-day-old rats. (PsycINFO Database Record (c) 2010 APA, all rights reserved)