A study of the interface between bone and acrylic cement by scanning electron microscopy

The influence of different pretreatments upon locomotor stimulation, induced by injection of ergometrine into the nucleus accumbens of rats, was investigated. The noradrenergic antagonists phenoxybenzamine and propranolol and the serotonin antagonist methysergide produced no clear changes. Reserpine, alone or in combination with alpha-MPT, considerably shortened the delay between injection of ergometrine and start of locomotor stimulation. Ro-DOPA, but not Ro-5-HTP, clearly antagonized the locomotor stimulation. The effect of ergometrine was strongly diminished following injection of haloperidol directly into the nucleus accumbens. A strong inhibition was also observedfollowing intracerebral administration of the imidazoline derivative (3,4-dihydroxy-phenylamino)-2-imidazoline (DPI), but not after injection of the structurally related compound clonidine. DPI by itself and also the ergot derivatives ergocornine, bromocryptine, LSD, dihydroergotamine and methysergide in doses 5--10 times as high as that of ergometrine failed to produce locomotor stimulation following injection into the nucleus accumbens. The results are discussed, especially with regard to the role of dopamine.     

The role of dopamine in withdrawal jumping in morphine dependent rats

The role of dopamine (DA) in precipitated withdrawal jumping was studied in morphine dependent rats. Pretreatment with various dopaminergic agonists induced a dose-dependent increase in naloxone induced jumping. Pimocide totally blocked the facilitatory effect of piribedil while naloxone induced jumping was not dose-dependently decreased. Biochemical measurements revealed that during precipitated withdrawal the level of DA was elevated and the accumulation of 3,4-dihydroxy-phenylacetic acid (DOPAC) and homovanillic acid (HVA) after probenecid as well as the level of 3-methoxytyramine in the striatum was reduced. Unilateral inactivation of the caudate by local injection of KCl induced contralateral circling during withdrawal. Additional systemic haloperidol pretreatment did not change the direction of circling while additional apomorphine pretreatment changed the direction to ipsilateral and increased the circling rate highly. These latter as well as the biochemical findings strongly suggest an inhibition of striatal DA-mechanisms during withdrawal. The apparent contradiction of these findings to the above finding showing a facilitatroy role of DA-agonists on jumping is discussed.     

The elastic cartilage in the normal rat epiglottis. I. Fine structure

Unilateral electrolytic lesions of the locus coeruleus in rats result in spontaneous ipsiversive rotation, which is then replaced by contraversive rotation. One week after lesioning, when spontaneous turning ceases, apomorphine and d-amphetamine elicit contraversive circling behaviour, which was not affected by noradrenergic receptor blockade but was abolished by dopamine receptor blockade. The drug-induced contraversive circling response was also reproduced by piribedil but not clonidine. Combined unilateral electrolytic locus coeruleus and substantia nigra lesions on the same side resulted in apomorphine- and d-amphetamine-induced ipsilateral rotational behaviour which was indistinguishable from that seen with substantia nigra lesions alone. In rats with unilateral locus coeruleus lesions, the dose of intrastriatally injected apomorphine required to produce circling was less on the lesioned than the non-lesioned side. Direct injection of noradrenaline into one substantia nigra caused contraversive circling. Direct injection of phenoxybenzamine into one substantia nigra followed by apomorphine caused ipsiversive circling. The results suggest that the circling behaviour seen after unilateral locus coeruleus lesions depends on an asymmetry of striatal dopamine receptor activity and are consistent with a proposed coeruleus-nigral noradrenergic pathway, which enhances impulse flow in the dopaminergic nigrostriatal system.     

The relationship between striatal and mesolimbic dopamine dysfunction and the nature of circling responses following 6-hydroxydopamine and electrolytic lesions of the ascending dopamine systems of rat brain

The importance of extrapyramidal and mesolimbic function for circling behaviour was investigated by placing 6-hydroxydopamine (6-OHDA) and electrolesions in the cell bodies, axons and terminals of each system. Circling behaviour was weak when 6-OHDA was placed at the centre of the substantia nigra (SN), but the characteristic contralateral/ipsilateral turning to apomorphine/amphetamine were recorded. Circling was more marked when 6-OHDA was placed anterior to the SN but was generally absent following injections posterior to the SN. However, 6-OHDA placed in the medial forebrain bundle in the lateral hypothalamus resulted in intense contralateral/ipsilateral turning to apomorphine/amphetamine. Generally, the intensity of circling responses was related to the degree of striatal dopamine (DA) depletion but the more effective lesions also caused reductions in mesolimbic DA content. However, circling was not observed following any 6-OHDA injection into the mesolimbic DA system and it is concluded that mesolimbic DA function is not essential for the initiation of circling. In contrast to the 6-OHDA lesions, rats circled ipsilateral to both apomorphine and amphetamine when the SN was damaged by electrocoagulation to cause marked depletion of striatal dopamine. Lesser depletions of striatal dopamine after electrocoagulation in different regions of the medial forebrain bundle were associated with a lower intensity of ipsilateral circling to both drugs. In general, the differences between 6-OHDA and electrolesions could not be explained by additional damage to ascending noradrenaline or 5-hydroxytryptamine pathways. Lower doses of apomorphine were effective in the 6-OHDA circling rats, and the ipsilateral striatum of such rats was more sensitive to directly applied DA. Higher doses of apomorphine were required to produce circling after chronic electrolesions which rendered the ipsilateral striatum insensitive to DA. The contralateral circling to apomorphine after 6-OHDA lesions was abolished by chronic but not by acute electrolesion of the SN. It is suggested that electrolesions of the SN cause different effects to 6-OHDA because they destroy neuronal pathways in addition to the dopaminergic nigrostriatal tract. These appear to be required for the expression of circling behaviour caused by stimulation of the denervated striatum. Whereas 6-OHDA lesions result in super-sensitivity of the denervated strital DA receptors, electrolesions may cause a hypo-sensitivity of the same receptor sites.     

Inhibition of acoustic priming in mice

Mice of the C57BL/6J strain can be made susceptible to audiogenic seizures by a process known as acoustic priming. Acoustic priming can be blocked when the animals are injected either with puromycin or with puromycin aminonucleoside before the application of the priming stimulus. Cycloheximide, diphenylhydantoin, and d-amphetamine had little effect on priming-induced audiogenic seizures in these animals. All of these drugs, however, when given in combination with puromycin reversed in the protective action of puromycin against audiogenic seizures. Puromycin administered to 19-day-old mice increased susceptibility to electroconvulsive seizures when the animals were tested at 22 days of age. It is suggested that puromycin is able to block priming-induced audiogenic seizures by producing abnormal electrical activity in the brain or through an interference with normal neurohumoral transmission by incomplete peptides.     

Audiogenic seizures in curarized mice

Previous experiments have indicated that interference with somatosensory feedback from convulsive movements may lessen the severity of audiogenic seizures in susceptible rodents. For further investigation of this phenomenon, mice were partially immobilized with tubocurarine chloride to attenuate convulsive movements and somatosensory input associated with such movements. In Experiment 1, seizures of mice injected with .15 mg/kg were evaluated behaviorally and compared with seizures of saline-injected litter-mates. The likelihood of clonic-tonic seizures in curarized mice was as high as that of control mice, although convulsive movements were somewhat less violent and seizure fatalities were markedly reduced. In Experiment 2, seizures of mice given .25 mg/kg were evaluated with electroencephalography, and records were compared with those of controls. Despite the near absence of behavioral signs of convulsions, electroencephalograms of curarized mice showed that audiogenic seizures readily occurred. The findings suggest that audiogenic seizures are centrally "programmed" and do not require feedback from convulsive movements. However, it may be possible to disrupt the central "program" by introducing appropriate somatosensory input not normally encountered during audiogenic seizures.     

Auditory physiology and behavior in RB/1bg, RB/3bg, and their F? hybrid mice (Mus musculus): Influence of genetics, age, and acoustic variables on audiogenic seizure thresholds and cochlear functions.

Examined behavioral and cochlear functions in mice inbred for audiogenic seizure susceptibility and resistance. The cochlear action potential (AP) thresholds of the susceptible RB/1bg inbred mice were abnormally high, and the resistant inbred RB/3bg mice had normal AP audiograms. The F? hybrid showed heterosis for its cochlear function. Only the RB/1bg was susceptible to audiogenic seizures on the 1st acoustic exposure. (25 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Electroencephalographic correlates of audiogenic seizures during ethanol withdrawal in mice

C57BL/6Bg mice had silver bead electrodes chronically implanted on the surface of the cortex and had their cortical EEG recorded during audiogenic seizures following ethanol withdrawal. For 7 days, the experimental groups were fed a liquid diet containing 6% v/v ethanol ad lib as the only source of food and water. The control group was fed a similar diet containing an isocaloric amount of sucrose. The cortical EEG's of experimental and control groups before, during, and after treatment were virtually identical. Only the experimental group was susceptible to audiogenic seizures. During audiogenic seizures, the cortical EEG showed no sign of spike waves or paroxysmal activity. This is in contrast to picrotoxin convulsions with these same mice as well as to spontaneous convulsions in animals following ethanol withdrawal. Similar EEG observations have been reported on audiogenic seizures from genetic and acoustically primed susceptibilities. Consequently, we suggest that all audiogenic seizure responses, including those during ethanol withdrawal, are a type of subcortical epilepsy.     

Middle cerebral artery aneurysm complicated by tuberculosis

Pentazocine, a kappa opioid receptor agonist, induced catalepsy in mice suggesting thereby that it might possess postsynaptic striatal D 2 dopamine (DA) receptor blocking activity. However, our other findings, that pentazocine pretreatment did not antagonise the cage climbing behaviour induced by the directly acting DA agonist apomorphine in mice and actually potentiated the stereotyped behaviour induced by the indirectly acting DA agonist methamphetamine in mice, indicate that pentazocine does not possess postsynaptic striatal and mesolimbic D 2 DA receptor blocking activity. Pretreatment with naloxone, an antagonist of opioid receptors, antagonised pentazocine-induced catalepsy. This suggests the possible involvement of opioid mechanisms in the induction of catalepsy by pentazocine in mice.     

Vaccination against ergot alkaloids and the effect of endophyte-infected fescue seed-based diets on rabbits

Three sequential experiments were conducted with rabbits to 1) determine the effect of endophyte-infected (E+) tall fescue seed on rabbit performance and examine the effect of anti-ergot alkaloid immunization on rabbit performance and protectiveness against fescue toxicosis, 2) compare immunogens designed to elicit systemic anti-ergot alkaloid antibodies, and 3) select a superior adjuvant. In Exp. 1, rabbits (n = 6/treatment) fed E+ fescue seed diets (20%, 340 ppb total ergot alkaloids) had reduced (P < .05) intake and weight gain compared with endophyte-free (E-) controls, whereas apparent diet digestibility was not different between E+ and E-. Rabbits immunized against ergot alkaloids (E+ vac) with lysergol conjugated to human serum albumin (Ly-HSA) had greater (P < .05) intake than E+ rabbits during the wk 1 of a 3-wk dietary challenge. In Exp. 2, rabbits (n = 4/treatment) were immunized with Ly-HSA, with H100-B (ergot alkaloid hapten, H100-different protein carrier, B conjugate), or combinations of both with alum as adjuvant. Greatest (P < .001) anti-ergot alkaloid antibody (Ab) titer developed in the group immunized with H100-B. In Exp. 3, rabbits (n = 4/treatment) were immunized with the immunogen H100-B in conjunction with six adjuvants. Freund's incomplete adjuvant (FIA) in combination with DEAE-dextran and FIA alone gave highest anti-ergot titers. In summary, rabbit weight gain and intake were reduced by feeding E+ fescue seed diets, immunization against ergot alkaloids provided temporary improvement in intake, and H100-B conjugate with FIA or FIA + DEAE-dextran as adjuvants elicited a superior anti-ergot immune response. We believe that rabbits may serve as a model animal for fescue toxicosis research.     

Reduction of dopamine synthesis inhibition by dopamine autoreceptor activation in striatal synaptosomes with in vivo reserpine administration

In an attempt to clarify the mechanisms by which dopamine (DA) autoreceptor activation inhibits DA synthesis, the efficacy and potency of the D2 DA agonists bromocriptine, lisuride, and pergolide, and the D1-D2 DA agonist apomorphine were studied in rat striatal synaptosomes, in which the rate of DA synthesis (formation of 14CO2 from L-[1-14C]tyrosine) was increased 103% by treating the animals from which the synaptosomes were obtained with reserpine (5 mg/kg i.p. twice, 24 and 2 h before they were killed), using the striatal total homogenate as the standard synaptosomal preparation. The increase in DA synthesis evoked by reserpine was additive with that produced by treatment of the synaptosomes with dibutyryl cyclic AMP, suggesting that, not a cyclic AMP-dependent, but possibly a Ca(2+)-dependent mechanism was involved. The DA agonists showed a concentration-dependent inhibition of DA synthesis in the control synaptosomes, which was antagonized by the selective D2 DA antagonist (-)-sulpiride. In the synaptosomes with increased rate of DA synthesis obtained from the rats treated with reserpine, the concentration-response curves of DA synthesis inhibition for the other DA agonists were shifted to the right, and the effect of bromocriptine was completely eliminated, whereas bromocriptine antagonized the effect of apomorphine. The increased rate of DA synthesis was not preserved in the striatal P1 + P2 fraction obtained from the reserpine-treated rats, but the effects of the DA agonists were still reduced to the same degree as those in the total homogenate. (-)-Sulpiride did not enhance DA synthesis in synaptosomes from the reserpine-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)     

Auditory similarities associated with genetic and experimental acoustic deprivation.

In previous studies, susceptibility to audiogenic seizures has been produced in otherwise nonsusceptible mice by acoustic stress and by conductive hearing loss. Both procedures temporarily elevate the absolute threshold of the auditory evoked potential (AEP) and are maximally effective during a circumscribed period of early development. The present 2 experiments were conducted with 35 DBA/2J and 36 C57BL/6J mice. In the genetically susceptible DBA/2J mouse, AEP thresholds indicated that its auditory system was functionally less mature during this early period than that of the nonsusceptible C57BL/6J mouse. It is proposed that innate susceptibility found in the DBA/2J mouse results from auditory disuse supersensitivity during a critical developmental period, in support of the hypothesis (J. C. Saunders et al) for acoustically primed mice. The increased peak-to-peak AEP amplitudes, however, were not believed to be causally related to the audiogenic seizures. (28 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effects of neonatal thyroxine, genotype, and noise on the ear and audiogenic seizures.

T. N. Seyfried et al (1979) recently reported that the DBA/2J mouse genotype, which is innately susceptible to audiogenic seizures, has high neonatal levels of thyroxine (T?) and that neonatal injections of T? induced susceptibility in the C57BL/6J mouse. In the experiment, neonatal T? injections (20 μg) produced a temporary peripheral auditory dysfunction that appeared to be conductive in nature in the C57BL/6J mouse (n?=?106). A cochlear dysfunction was also seen in the DBA/2J mouse (n?=?17) and in the acoustically primed C57BL/6J mouse. Since a peripheral auditory threshold elevation in these latter groups of mice appears to be causally related to their susceptibility to audiogenic seizures, it is likely that at least a portion of the susceptibility that Seyfried et al reported was due to the effects of T? on the ear. (34 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Pharmacogenetic differences in audiogenic seizure priming of C57BL/6Bg and DBA/1Bg-asr mice

Susceptibility to audiogenic seizures can be induced in some strains of resistant mice by exposure to an initial auditory stimulus (acoustic priming). Aminooxyacetic acid, hydrazine, glutamic acid, gamma-aminobutyric acid (GABA), cycloheximide, and metyrapone antagonize the acoustic priming of audiogenic seizure susceptibility in C57BL/6Bg mice, whereas only metyrapone attenuates that of DBA/1Bg-asr mice. The strain difference in the effect of AOAA and cycloheximide is correlated with a small, transient fall in level of brain GABA in C57BL/6Bg but not DBA41Bg-asr mice. These findings support our hypothesis that there are at least two neural mechanisms of acoustic priming, each with its own genetic basis and that corticosteroids are required by both mechanisms for the development of primed seizures.     

Anticonvulsant and proconvulsant roles of nitric oxide in experimental epilepsy models

The effect of acute (120 mg/kg) and chronic (25 mg/kg, twice a day, for 4 days) intraperitonial injection of the nitric oxide (NO) synthase (NOS) inhibitor NG-nitro-L-arginine (L-NOARG) was evaluated on seizure induction by drugs such as pilocarpine and pentylenetetrazole (PTZ) and by sound stimulation of audiogenic seizure-resistant (R) and audiogenic seizure-susceptible (S) rats. Seizures were elicited by a subconvulsant dose of pilocarpine (100 mg/kg) only after NOS inhibition. NOS inhibition also simultaneously potentiated the severity of PTZ-induced limbic seizures (60 mg/kg) and protected against PTZ-induced tonic seizures (80 mg/kg). The audiogenic seizure susceptibility of S or R rats did not change after similar treatments. In conclusion, proconvulsant effects of NOS inhibition are suggested to occur in the pilocarpine model and in the limbic components of PTZ-induced seizures, while an anticonvulsant role is suggested for the tonic seizures induced by higher doses of PTZ, revealing inhibitor-specific interactions with convulsant dose and also confirming the hypothesis that the effects of NOS inhibitors vary with the model of seizure.     

Brain dopamine and seizure susceptibility in mice

In electroshock test apomorphine appeared without effect, D, L-amphetamine and L-DOPA (in a high dose) elevated the convulsive threshold, while amantadine decreased it. Among investigated dopamine (DA) receptor blockers spiperone, pimozide and fluphenazine lowered the threshold, haloperidol being without effect. The convulsive threshold elevated by L-DOPA was not affected by neuroleptics and phentolamine but on the other hand DA receptor blockers and phentolamine anatagonized the effect of D, L-amphetamine. The effect of amantadine was not influenced by neuroleptics. In pentylenetetrazol (PTZ) test only amantadine and L-DOPA (in high doses) affected the threshold, increasing seizure susceptibility; the above effect was not abolished by pimozide. Our results seem to indicate that the activity of brain DA system seems not to be involved directly in the susceptibility to electrogenic or PTZ-induced seizures in mice.     

Pinna reflex thresholds and audiogenic seizures: Developmental changes after acoustic priming.

Exposed 200 16-day-old C57BL/6J mice to 30 sec. of 120-db noise (acoustic priming). Primed Ss and 220 unprimed Ss were tested on subsequent days for either audiogenic seizures or an altered threshold to the Preyer pinnal reflex. Within 24 hr., the Preyer reflex threshold had decreased in primed Ss by 5.4 db., and a further decline of 10.1 db. occurred over the next 4 days. The 2 indices of audiogenic seizures did not show a corresponding change until the 2nd day after priming. It is hypothesized that acoustic priming selectively disrupts inhibitory mechanisms which normally protect the CNS from an overload by intense sounds, and that audiogenic seizures and the Preyer reflex are independently affected by this common event. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Roles of anoxia and noise-induced hearing loss in the postictal refractory period for audiogenic seizures in mice.

Three experiments with 188 Ss demonstrated a postictal refractory period for audiogenic seizures in DBA/2J mice, which was not related to hearing loss but apparently was related to anoxia. Exp I controlled for the effects of noise exposure upon hearing sensitivity and demonstrated reduced susceptibility to subsequent audiogenic seizures for at least 1 hr after initial clonic-tonic convulsions. The postictal refractory period resulted from the occurrence of seizures per se, not from noise exposure alone. Exp II demonstrated deficiencies of sensorimotor functions that accompanied reduced postictal seizure susceptibility. The 2 phenomena had similar time courses of recovery, which suggested a common mechanism, probably anoxia, associated with the initial convulsions. In support of this view, Exp III shows that recovery from both phenomena was expedited by allowing Ss to breathe increased O-sub-2. The role of anoxia in fatal convulsions is suggested by the finding that Ss experiencing clonic-tonic convulsions in a high-O-sub-2 environment survived without exception. In contrast, seizures of air-breathing controls were almost always fatal. The data indicate that the postictal reduced susceptibility to audiogenic seizures was closely related to metabolic depletion (in particular, anoxia). The pattern of recovery of susceptibility further suggests that the effects of anoxia impair the spread of seizure activity through the CNS, although the initiation of seizures is also affected for a short time. (44 ref) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Characterization of the production of acetaldehyde by astrocytes in culture after ethanol exposure

Mice selected for large and small brain weights (LB and SB strains, respectively) were tested for audiogenic seizure sensitivity. We have examined 150 LB and 120 SB mice of the 13th and 14th generations. In mice of the 12th generation brain and body weight values were 498.6 +/- +/- 2.1 mg and 26.2 +/- 0.4 g, respectively, for the LB and 415.35 +/- 1.9 mg and 23.8 +/- 0.3 g for the SB, the difference being significant for both values (p < 0.001). The SB mice revealed higher audiogenic sensitivity (larger proportion of seizures and deaths) at the age of 22-27 days. Adult LB mice were more sensitive than SB of the same age (irrespective of whether they received priming stimulation or not). The obtained evidence is discussed in the context of differences between audiogenic fits and other seizure states.     

The effect of nigral implantation on sensitization to dopamine agonists in 6-hydroxydopamine-lesioned rats

The implantation of fetal nigral tissue into the striatum of patients with Parkinson's disease is a promising approach to treatment which may produce clinical benefit partly by influencing drug responsiveness. The purpose of the present study was to determine the pharmacological mechanisms which drug response changes by measuring to what extent sensitization produced by repeated apomorphine treatment was attenuated by tissue implantation in rats with nigrostriatal lesions. Prior to implantation of nigral cell suspensions, the daily administration of apomorphine to rats with unilateral 6-hydroxydopamine lesions produced a progressive increase in the magnitude and duration of rotational behaviour. After implantation, apomorphine-induced rotational effects were reduced to levels observed upon the initial exposure to drug and did not increase following repeated treatment. Attenuated responses to selective D1 and D2 agonists were also observed after implantation. In vehicle-implanted rats, the initial response to apomorphine was attenuated but then increased following repeated apomorphine administration. No attenuation in responses to selective D1 and D2 agonists was observed in this group. Cell suspensions prepared from fresh and cyropreserved tissue produced similar behavioural effects, even though the volume of transplanted striatum exhibiting tyrosine hydroxylase activity was greater with fresh tissue. The duration of rotational behaviour induced by apomorphine was not affected by cell implantation. These findings suggest that the expression of sensitization in an animal model of parkinsonism may disappear after a period without drug treatment. Implantation of nigral tissue may produce beneficial results in parkinsonism by limiting the development of dopamine agonist-induced sensitization.