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Effects of prenatal spaceflight on vestibular responses in neonatal rats.

Ten pregnant Norway rats (Rattus norvegicus) were flown for 11 days on board the NASA space shuttle from gestational day 9 (launch) until gestational day 20 (landing) of the rats' 22-day pregnancy. After the birth of the pups, vestibular responses were analyzed from postnatal day (P) 0 until P5. In the first test, P0 neonates were supported on a platform in a side-lying position. Skyward head movements (i.e., movements performed against the gravity vector) were more frequent than head movements toward Earth in both flight and control neonates. In the second test, the contact-righting reflex, composed of stereotyped movements that rotate the body from supine to prone on a solid surface, was analyzed in P0 neonates. The frequency and latency of contact-righting responses did not differ in flight and control neonates. In the third test, vestibular head righting, with tactile and proprioceptive cues removed, was tested in neonates on P1, P3, and P5 by using a water-immersion test. Righting responses were observed less frequently in P1 and P3 flight neonates compared with controls. However, this deficit was transient, as evidenced by complete response recovery on P5. Collectively, these findings provide evidence for a selective disruption of vestibular-mediated responses after prenatal exposure to spaceflight.

Animals↗

Acetazolamide and amiloride inhibit pentobarbital-induced facilitation of nocifensive reflexes.

BACKGROUND: Neuronal excitation may result from stimulation of gamma-aminobutyric acid A (GABA(A)) receptors that prolong the channel opening, depolarizing the postsynaptic membrane. Drugs such as acetazolamide or amiloride can block GABA depolarization. Barbiturates facilitate nociceptive reflexes and also prolong the GABA(A) channel open-time. To evaluate the possible mechanism, the authors studied the impact of acetazolamide and amiloride on pentobarbital-induced nocifensive reflex facilitation. Because nitric oxide (NO) is a mediator of reflex facilitation, the authors evaluated the effects of NO synthase inhibition. METHODS: Nocifensive reflex thresholds were quantified with the hind paw withdrawal latency from radiant heat (HPW latency) in the rat. Nocifensive reflexes were facilitated with intraperitoneal injection of pentobarbital (30 mg/kg). The authors tested the roles of GABA-mediated depolarization and NO in reflex facilitation by pretreatment with acetazolamide and amiloride and inhibition of NO synthase with L-NAME and 7-NI, respectively. Sedative effects of pentobarbital were evaluated with the righting reflex, the response to vibrissal stimulation, and plasma drug concentrations. RESULTS: Pentobarbital decreased the hind paw withdrawal latency from 11.2+/-1 to 8.3+/-1 s (P < 0.001). Pretreatment with each of the four test drugs limited the reduction in reflex facilitation after pentobarbital to 1.3 s or less, similar to the reduction seen after saline injection, without altering sedation. L-NAME increased plasma pentobarbital concentrations by 10% without changing the concentration associated with return of responsiveness. CONCLUSIONS: Pentobarbital-induced nocifensive reflex facilitation was inhibited by all four tested drugs without evidence of increased sedation. The results are consistent with a role for GABA(A) receptor-mediated depolarization in barbiturate-induced hyper-reflexia.

Acetazolamide↗

Effects of nutritional factors on reproduction, growth, preweaning reflex development and postweaning learning performance in SHRSP.

1. Dietary high protein intake in stroke-prone spontaneously hypertensive rats (SHRSP) induces a reduction of blood pressure and decreases the incidence of cerebral lesion. The objective of this investigation was to determine the effects of nutritional factors of dietary high protein on reproduction, growth, preweaning reflex development, postweaning behaviour and learning performance in SHRSP. 2. SHRSP were fed on a high protein rat diet (OA2 diet) and a standard rat diet for SHRSP (FSP diet). Rats were mated by brother-sister combinations and observed on reproductive performance, preweaning reflex development and postweaning learning performance among the 3rd to the 6th generations. 3. OA2 showed some advanced responses at the preweaning period compared to FSP in the surface righting, negative geotaxis and mid-air righting reflexes. 4. At the postweaning period, hyperactivity of OA2 was indicated at the open field test. In the ambulatory activity of the circadian rhythm, OA2 was better synchronized with running activity in the light and dark alternation cycle. 5. OA2 group indicated the higher postweaning learning performance in the water E, the water multiple T (Biel) and the Morris water-maze test as well as the acquisition of the conditioned avoidance response test. 6. In conclusion, dietary high protein intake in SHRSP produced some advanced effects on preweaning reflex development and postweaning learning performance.

Animal Nutritional Physiological Phenomena↗

Comparative study of three intramuscular anaesthetic combinations (medetomidine/ketamine, medetomidine/fentanyl/midazolam and xylazine/ketamine) in rabbits.

OBJECTIVE: To compare the quality of surgical anaesthesia and cardiorespiratory effects of three intramuscular (IM) anaesthetic combinations in rabbits. STUDY DESIGN: Prospective randomized cross-over experimental study. ANIMALS: Nineteen adult female chinchilla mixed-bred rabbits weighing 3.9 +/- 0.8 kg. METHODS: Rabbits were given one of three IM anaesthetic combinations: 0.25 mg kg(-1) medetomidine and 35.0 mg kg(-1) ketamine (M-K), 0.20 mg kg(-1) medetomidine and 0.02 mg kg(-1) fentanyl and 1.0 mg kg(-1) midazolam (M-F-Mz) and 4.0 mg kg(-1) xylazine and 50 mg kg(-1) ketamine (X-K). The effects of anaesthesia on nociceptive reflexes, circulatory and respiratory function were recorded. Statistical analyses involved repeated measures anova with paired Student's t-test applied post hoc. P-values <0.05 were considered as significant. RESULTS: Reflex loss was most rapid and complete in M-K recipients, whereas animals receiving M-F-Mz showed the longest tolerance of endotracheal intubation (78.1 +/- 36.5 minutes). Loss of righting reflex was significantly most rapid (p < 0.05) in the X-K group (114.7 +/- 24.0 minutes). Surgical anaesthesia was achieved in 16 of 19 animals receiving M-K, in 14 animals receiving M-F-Mz, and in seven animals with X-K, but only for a short period (7.1 +/- 11.6 minutes). This was significantly (p < 0.001) shorter than with M-K (38.7 +/- 30.0 minutes) and M-F-Mz (31.6 +/- 26.6 minutes). Heart rates were greatest in X-K recipients; lowest HR were seen in animals receiving M-F-Mz. Mean arterial blood pressure was significantly higher (about 88 mmHg) during the first hour in the M-K group. During recovery, the greatest hypotension was encountered in the X-K group; minimum values were 53 +/- 12 mmHg. Six of 19 animals in the M-F-Mz group showed a short period of apnoea (30 seconds) immediately after endotracheal intubation. Respiratory frequency was significantly lower in this group (p < 0.001). Highest values for arterial carbon dioxide partial pressures (PaCO(2)) (6.90 +/- 0.87 kPa; 52.5 +/- 6.5 mmHg) occurred after induction of anaesthesia in group M-F-Mz animals. There was a marked decrease in PaO(2) in all three groups (the minimum value 5.28 +/- 0.65 kPa [39.7 +/- 4.9 mmHg] was observed with M-K immediately after injection). Arterial PO(2) was between 26.0 and 43.0 kPa (196 and 324 mmHg) in all groups during O(2) delivery and decreased - but not <7.98 kPa - on its withdrawal. Immediately after drug injection, pH(a) values fell in all groups, with lowest values after 30 minutes (7.23 +/- 0.03 with M-K, 7.28 +/- 0.05 with M-F-Mz, and 7.36 +/- 0.04 with X-K). The X-K animals showed significantly (p < 0.001) higher pH values than medetomidine recipients. During 1 hour of anaesthesia pH values in the medetomidine groups remained below those of the X-K group. CONCLUSIONS: Surgical anaesthesia was induced in most animals receiving medetomidine-based combinations. Arterial blood pressure was maintained at baseline values for about 1 hour after M-K. Transient apnoea occurred with M-F-Mz and mandates respiratory function monitoring. Oxygen enrichment of inspired gases is necessary with all three combinations. Endotracheal intubation is essential in rabbits receiving M-F-Mz. CLINICAL RELEVANCE: The quality of surgical anaesthesia was greatest with M-K. All combinations allowed recoveries of similar duration. It is theoretically possible to antagonize each component of the M-F-Mz combination.

Anesthesia↗

Electrophysiological and behavioral effects of ethanol on crayfish.

The effects of EtOH on the crayfish Procambarus clarkii and P. simulans were examined behaviorally in vivo and electrophysiologically in vitro on pre- and postjunctional mechanisms of synaptic plasticity at opener excitor nerve-muscle junctions. Addition of 75 mM EtOH to the bath water of holding tanks produced 47 to 54 mM EtOH levels in the hemolymph (blood) within 24 hr. These hemolymph EtOH levels were maintained for weeks by daily changes of the bath water containing 75 mM EtOH. After 24 hr of exposure to 75 to 150 mM EtOH in vivo, crayfish showed behavioral signs of intoxication as measured by a significant increase in righting reflex times and a significant decrease in tail-flip escape behavior. After 2 weeks of chronic exposure to 75 mM EtOH, crayfish showed behavioral tolerance as measured by a decrease in righting time and an increase in tail-flip escape behavior to control levels. EtOH applied acutely to opener nerve-muscle preparations in vitro at 10 to 100 mM concentrations produced an increased probability of transmitter release as measured by an increased frequency of spontaneous release of transmitter quanta and an increased amplitude of facilitated synaptic potentials evoked by 10 to 40 Hz stimulation of the excitor axon. Acute application of 300 to 600 mM EtOH resulted in a decreased amplitude of facilitated synaptic potentials due primarily to a decrease in postsynaptic input resistance. These data suggest that EtOH has a concentration-dependent biphasic effect on synaptic transmission.

Animals↗

Effects of prenatal ethanol exposure on physical growth, sensory reflex maturation and brain development in the rat.

In the offspring of ethanol-treated rats during gestation (25% ethanol in drinking water) decreased litter size, increased postnatal mortality rate, reduced body weight and body size, delayed ear opening, eyelid opening and teeth eruption, retarded air righting reflex acquisition, impaired brain growth, reduced cortical thickness and delayed maturation of layer Vth's pyramidal neurons: reduced basilar dendritic arborization and decreased number of spines in the apical dendrite, were observed when compared with age-matched controls fed with a standard diet. Minimal effects were found in the offspring of fibre-treated rats during gestation (standard diet mixed with cellulose) in which the body weight was similar to that of controls, although both the calorific intake from food and the mother's weight gain during pregnancy were similar to those of the ethanol-treated group. All these abnormal parameters became normal at the end of the first month of postnatal life, indicating recovery of these developmental defects produced by prenatal ethanol consumption.

Animals↗

Haloperidol exaggerates proprioceptive-tactile support reflexes and diminishes vestibular dominance over them.

Rats made immobile and cataleptic by haloperidol, a dopamine receptor blocker, maintain their static stable equilibrium by employing a variety of allied postural support reflexes. Under some test conditions, competition between such reflexes occurs, and in haloperidol-treated rats, unlike undrugged controls, proprioceptive-tactile stimuli appear to be dominant over vestibular stimuli. We investigated this relationship in rats by testing their air-righting with and without simultaneous contact of the tail on a wooden platform. The rats were lightly held in a supine position by the shoulders and pelvis, with or without tail contact on a small wooden platform 47 cm above the ground. Undrugged rats showed the normal pattern of righting which involves axial rotation with cephalocaudal recruitment whether the tail is contacting the platform or not. Upon release, the haloperidol-treated rats (2.5 mg/kg) gripped the platform with their tail, which interfered with the air-righting reflex. This demonstrates that in haloperidol-treated rats, the dominance of tactile-proprioceptive postural support reflexes over those triggered vestibularly.

Animals↗

Nocifensive reflex thresholds in rats: measures of central nervous system effects of barbiturates.

PURPOSE: To characterize the pharmacodynamic relationships between plasma pentobarbitone and thiopentone concentrations and nocifensive reflexes during emergence from anaesthesia. METHODS: Forty-nine rats were studied. Plasma barbiturate concentrations were measured with high performance liquid chromatography. Nocifensive reflexes were assessed with the hindlimb withdrawal latency (WL) to heat and the somatic motor response threshold (SMRT) to tail pressure. In Protocol I, SMRT, WL, sedation, and the presence of paw-licking and the righting reflex were assessed in unrestrained rats before and every 10 min for two hours after an intraperitoneal injection of pentobarbitone (30 mg.kg-1). Plasma pentobarbitone kinetics were determined in a separate group of rats. In Protocol II, SMRT and drug concentrations were measured concurrently in partially restrained animals before and for 35 min after a computer-controlled i.v. bolus of thiopentone. In Protocol III the SMRT-plasma thiopentone relationship was determined during increasing and decreasing plasma thiopentone concentrations. RESULTS: Enhancement of both nocifensive reflexes was observed in the unrestrained animals. Enhancement of SMRT was maximal [175% (153-197) of control values] at a mean plasma thiopentone concentration of 11 (9-13) micrograms.ml-1. The SMRT-plasma thiopentone curve showed a mean efflux-influx difference in plasma thiopentone concentration of 4(2.3-5.7) micrograms.ml-1. CONCLUSIONS: Barbiturate-associated nocifensive reflex enhancement occurs in unrestrained animals with both thermal and pressure stimuli. The SMRT-plasma thiopentone concentration relationship during emergence from anaesthesia was similar to that observed previously during induction. The thiopentone plasma concentration-SMRT plot showed an equilibrium delay similar to that previously described by others for thiopentone at an electroencephalographic effect site.

Animals↗

A prospective study of three postural reactions.

In order to assess the evolution of postural reactions in the prone position, a group of 149 normal infants were followed from birth to two years of age. The Landau reflex was present in 44 per cent of two-month-old infants, and in 95 per cent at four months. The tonic labyrinthine response (grades 2 to 4) was seen in 80 per cent of infants at two weeks, with a marked diminution by the age of 24 months. In contrast, the symmetrical tonic neck reflex was detected in fewer than 30 per cent of the infants: the maximum prevalence was at four to six months of age. These findings are consistent with the hypothesis that the Landau is an early righting reflex which emerges after, and is independent of, the tonic labyrinthine response in prone and the symmetrical tonic neck reflex.

Female↗

Sertraline delays the somatic growth and reflex ontogeny in neonate rats.

This study investigated the somatic maturation and ontogeny of reflexes in neonate rats treated with sertraline (Sert) during the suckling period. The animals were divided into four groups; three that received daily doses of Sert (5, 10 or 15 mg/kg s.c.; groups Sert5, Sert10, and Sert15, respectively), and a fourth group that received distilled water (Dw) (1 ml/kg/b.w.). Growth indicators (body weight, axis of the head and tail length) were measured daily, from the 1st to the 21st postnatal day. The reflexes (righting, free-fall righting, negative geotaxis, cliff avoidance, auditory startle response, vibrissa placing and palm grasp) and physical-feature maturation (ear unfolding, auditory conduit opening, irruption of the lower incisors and eye opening) were recorded each day of the animal's life. All groups were compared to the Dw group. The body weight gain was reduced in all the Sert groups. Moreover, a delay in the growth of the body length was observed in all the Sert groups. Higher Sert doses reduced the speed of growth in the tail length. The medio-lateral head axis reduced in Sert15 and Sert5 doses. Otherwise, Sert10 had a temporary acceleration in this growth, but the growth of the anteroposterior head axis had a delay in all the Sert groups. The highest doses induced a delay in physical-feature maturation. The palm grasp reflex (disappearance) was retarded in Sert10; cliff avoidance advanced in Sert10; negative-geotaxis and free-fall righting retarded in Sert15. The findings suggest that altered serotonergic system activity induced by sertraline early in life could play a role in the retardation of the somatic growth ontogeny as well as a delay in the maturation of some reflexes.

Animals↗

Cross-generational effect of prenatal morphine exposure on neurobehavioral development of rat pups.

Prenatal exposure to opiates can have devastating effects on the development of human fetuses and may induce long-term physical and neurobehavioral changes during postnatal maturation. The present study was aimed at identifying cross-generational effects of prenatal morphine exposure in Sprague-Dawley rats. Pregnant rats were injected subcutaneously with either saline or morphine (10 mg/kg) twice daily during gestational days 11-18. Litter size, percentage of males and females, anogenital distances (AGDs), righting reflex, and body weight were assessed in prenatally morphine-exposed pups (first generation) and their offspring (second generation). Both prenatally morphine-exposed pups and offspring of prenatally morphine-exposed dams exhibited an increased latency to right. Additionally, second generation pups were slower in righting than first generation pups. During the early postnatal period the second generation pups weighed less than the first generation regardless of drug exposure. The AGDs of second generation male pups were decreased relative to the first generation. Our data provide important novel information about the trans-generational effects of maternal opiate abuse that may be useful for understanding/evaluating the teratogenic effects of prenatal opiate exposure.

Analgesics, Opioid↗

Treatment with methylazoxymethanol at different gestational days: physical, reflex development and spontaneous activity in the offspring.

Pregnant rats were injected with a single dose of methylazoxymethanol (MAM, 25 mg/kg) on gestational day 14, 15, 16, 17, 18 or 19 and offspring were tested for their physical development, reflex development and spontaneous activity. MAM treatment did not affect gestational and litter parameters at any of the time of administration studied. Treatment at gestational day 14 (GD14) had the most severe effect on functional neurodevelopment until weaning: righting reflex at surface, chimney test, horizontal wire test resulted altered. Administration at GD15, 16, 18, 19 did not affect the performance in these tests. Offspring treated at GD17 showed a delayed eye opening and an impaired performance in the horizontal wire test. When tested at 50 days of age on the rotarod, all the treated groups performed worse than controls with the exception of GD19 treated offspring. Administration at GD14 and GD15 resulted in increased spontaneous activity of the offspring at 21 days but not at 60 days of age. Different degrees of microencephaly were observed for all treated groups. The results indicate that alterations of physical and behavioral development induced by MAM treatment are dependent on the time of MAM administration, and specific behavioral tests are able to detect different abnormalities and differentiate among treatment groups. Some alterations observed in MAM rats undergo to adaptive changes during maturation of the CNS.

Animals↗

Modification of the actions of ethanol by centrally active peptides.

Ethanol (2.0-5.0 g/kg, IP) caused a dose-related impairment of the aerial righting reflex of mice 60 min after injection. Ethanol (3.5 g/kg, IP) given simultaneously with neurotensin (30 micrograms, IC), bombesin (30 micrograms, IC) or beta-endorphin (20 micrograms, IC) caused a greater impairment of the reflex than ethanol alone. Simultaneous treatment with ethanol (4.0 g/kg, IP) and thyrotropin-releasing hormone (TRH, 3.0-30 micrograms, IC) caused less impairment of this measure than ethanol alone. None of the peptides altered the height of aerial righting when administered alone, or when administered with ethanol no peptide altered blood or brain ethanol content. Unexpectedly, TRH (20 and 40 mg/kg, IP) potentiated the action of ethanol by increasing punished licking in water-deprived rats, rather than antagonizing this acute action of ethanol. Like ethanol (1.0 and 2.0 g/kg, IP), beta-endorphin (100 micrograms, IC) suppressed ethanol-withdrawal tremor and audiogenic-seizure susceptibility in ethanol-dependent rats. beta-Endorphin (1 microgram) and bombesin (10 and 30 micrograms, IC) reduced only audiogenic-seizure susceptibility. TRH (10-100 micrograms, IC, or 1-40 mg/kg, IV) and neurotensin (10-100 micrograms, IC) had no effect on these ethanol-withdrawal signs. These findings suggest that centrally active peptides may play a role in certain acute and chronic actions of ethanol. Because TRH, neurotensin, bombesin and beta-endorphin do not alter all actions of ethanol in the same way, an interaction of ethanol with many functionally independent neuronal circuits is suggested.

Animals↗

Behavioral reactions of the bat Carollia perspicillata to abrupt changes in gravity.

As part of an ongoing survey of the behavioral responses of vertebrates to abrupt changes in gravity, we report here on the reactions of bats (Carollia perspicillata) exposed to altered gravity during parabolic aircraft flight. In microgravity, mammals typically behave as if they were upside-down and exhibit repetitive righting reflexes, which often lead to long axis rolling. Since bats, however, normally rest upside-down, we hypothesized that they would not roll in microgravity. Only one of three specimens attempted to fly during microgravity. None rolled or performed any righting maneuvers. During periods of microgravity the bats partially extended their forearms but kept their wings folded and parallel to the body. Between parabolas and occasionally during microgravity the bats groomed themselves. Both the extended limbs and autogrooming may be stress responses to the novel stimulus of altered gravity. This is the first behavioral record of Chiroptera in microgravity.

Animals↗

Early behavioral development in the spontaneously hypertensive rat: a comparison with the Wistar-Kyoto and Sprague-Dawley strains.

The spontaneously hypertensive rat (SHR) is often used as a model for childhood attention-deficit/hyperactivity disorder (ADHD). To investigate behavioral maturation in SHR, body weight, age at eye opening, and performance in several behavioral tasks in male and female SHR, Wistar-Kyoto (WKY), and Sprague-Dawley rats were compared. SHRs were slower in performing the righting reflex on PND 4 and negative geotaxis compared with WKY and Sprague-Dawley. Both SHR and WKY were delayed relative to Sprague-Dawley in eye opening and beam walking. Rotarod performance was comparable in the 3 strains. Males were faster to right themselves than females, but there were no other significant sex differences nor Sex X Strain interactions. Delayed development in SHR may be related to a maturational delay observed in children with ADHD. Research assessing early behaviors in SHR, WKY, and other strains will help determine the most appropriate model for childhood ADHD and may help predict later behavioral dysfunction.

Age Factors↗

Indomethacin significantly reduces mortality due to acute ethanol overexposure.

Previous studies in our laboratory have demonstrated that indomethacin, a potent prostaglandin synthetase inhibitor, significantly antagonizes the depressant, activating, and hypothermic responses to ethanol. In this study, male SS mice, a line selectively bred for low sensitivity to the hypnotic effects of ethanol, were pretreated with indomethacin or vehicle up to 24 hr prior to administration of an LD69 dose of ethanol. Indomethacin pretreatment significantly reduced the mortality rate independent of pretreatment time and produced an increase in the number of animals exhibiting a depressed behavioral response as measured by loss of the righting reflex. These results suggest that indomethacin antagonized the effects of ethanol to an extent such that a lethal dose was transformed into a depressant dose. These data are consistent with our hypothesis that pretreatment with prostaglandin synthetase inhibitors serves to shift the ethanol dose response curve to the right, suggesting that the arachidonic acid cascade is an important system in the mechanism of ethanol's actions.

Alcoholic Intoxication↗

Differential effects on somatic and reflex development by chronic clomipramine treatment.

The developmental effect of altered 5-HT and NE levels is a subject that requires more attention, especially when considering the increased demand for antidepressive dual reuptake inhibitors. Serotonin and norepinephrine are bioamines that differentially influence the nervous tissue growth. This study investigated the somatic maturation and the ontogeny of reflexes in neonate rats treated from the 1st to the 21st postnatal day (PND) with clomipramine (20 mg/kg sc, daily), a potent monoamine reuptake inhibitor. Indicators of both general body growth (body weight, axis of the head and body lengths) and physical maturation (ear unfolding, auditory conduit opening, eruption of the lower incisors and eye opening) were appraised. Ontogeny of motor and sensory reflexes (righting, free-fall righting--acceleration, negative geotaxis, cliff avoidance, auditory startle response and vibrissa placing) was also observed. The results demonstrated that chronic neonatal treatment with clomipramine alters the somatic growth. However, it did not interfere with the onset time of many physical features and reflexes. These results provide insights into the consequences of dual transmitter during early development.

Age Factors↗

Effects of cyclophosphamide treatment of newborn mice on the development of swimming and reflex behavior and on adult behavioral performance.

Cyclophosphamide (CP), an antineoplastic agent, was administered subcutaneously to Swiss-Webster mice on the day of birth and the mice were later tested for developmental or adult behavioral abnormalities. The CP dosages of 20, 30, or 45 mg/kg of body weight retarded maturation of swimming ability and 45 mg/kg retarded maturation of the righting reflex. At 7 weeks of age mice treated neonatally with 30 or 45 mg/kg of CP had reduced locomotor activity and were more emotionally reactive than controls in an open field. Mice treated with 30 but not 20 mg/kg of CP tended to avoid shock less than controls and those treated with 20 mg/kg fell more frequently when crossing a rotating rod for food. Rotorod performance was improved by treatment with 45 but not 30 mg/kg of CP. All dosages examined decreased body weight gains but only 30 or 45 mg/kg resulted in gross body malformations. The results indicate that CP can functionally impair the development of mice and that some of these impairments are independent of gross body malformations.

Abnormalities, Drug-Induced↗