Biomedical subjects

T Archer

Publications and source records attributed to T Archer.

At least 73 records · Page 4Linked to original sources

PubMed1990

Learning deficits in aged rats pretreated chronically with barbital and tested late in abstinence: alleviation by tetrahydroaminoacridine.

Physostigmine and tetrahydroaminoacridine (THA) have been reported to improve cognitive function in patients with Alzheimer's disease. Two experiments were conducted to examine the effects of these anticholinesterase agents on learning in aged rats pretreated chronically with barbital. In the first experiment animals received barbital in their drinking water for 46 weeks. Controls were given only water. On days 100-104 of abstinence, when the animals were 20 months old, acquisition of the Morris maze task was initiated after treatment with physostigmine. It was found that physostigmine improved learning of the maze task in control but not barbital treated rats. In the second experiment animals received barbital solution or water as in experiment one. On days 100-103 of abstinence they were injected with THA before being tested in the Morris water maze. It was found that THA improved learning in both barbital treated and control rats. These results corroborate clinical findings of improved cognitive function following treatment with THA, and suggest that the therapeutic effects of THA may be mediated by mechanisms distinct from cholinesterase inhibition. Furthermore chronic barbital treatment could be used as a model to study cognitive disturbances in experimental animals.

Age Factors↗

PubMed1990

MPTP-induced hypoactivity in mice: reversal by L-dopa.

Three experiments were performed to study the subchronic effects of treatment with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 2 x 40 mg/kg subcutaneously two weeks before testing) in C57 BL/6 mice upon spontaneous motor activity and the reversal of the long-term behavioural changes by acute treatment with L-Dopa. Mice treated with MPTP showed a drastic reduction of striatal dopamine levels (-88%) associated with reductions of all three parameters of spontaneous motor activity, i.e. locomotion, rearing and total activity, during both the initial, exploratory, stage (first 90 min), and later stages of the 3- or 4-hr test periods. L-Dopa (5-80 mg/kg subcutaneously) injected 60 min. after the start of testing dose-dependently improved all three parameters studied in MPTP treated mice with 10 mg/kg being the lowest dose causing a significant effect, while doses above 20 mg/kg caused hyperactivity. During the initial period, rearing activity in MPTP mice was to a variable degree suppressed by the L-Dopa treatment (20-80 mg/kg); these reductions were followed by enormous increases in motor activity by the 40 mg/kg (locomotion) and 80 mg/kg (total activity) L-Dopa groups. Both the degree and duration of the L-Dopa-induced hypoactivity for locomotor behaviour increased dose-dependently in control mice. No suppressive effects of L-Dopa were obtained for total activity in control mice, although the 80 mg/kg L-Dopa doses evoked hyperactivity for up to 90 min. following treatment for both locomotion and total activity.(ABSTRACT TRUNCATED AT 250 WORDS)

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

PubMed1989

Selective lesion of central dopamine or noradrenaline neuron systems in the neonatal rat: motor behavior and monoamine alterations at adult stage.

Different parameters of motor behavior (locomotion, rearing and total activity counts) were studied in the adult rat following neonatal intracisternal 6-hydroxydopamine (6-OHDA, 50 micrograms) treatment combined with noradrenaline (NA) uptake blocker (desipramine) or dopamine (DA) uptake blockers (amfolenic acid or GBR 12909) to obtain selective DA or NA lesions respectively. At 61-65 days of age, selective DA-lesioned animals showed an initial decrease in spontaneous motor behavior at test days 1 and/or 2, while at test days 4 and 5 hyperactivity was observed. However, following amfolenic acid or GBR 12909 pretreatment leading to a selective NA lesion, no difference in spontaneous motor behavior was seen on any of the 5 test days. Determination of regional brain levels of NA and DA confirmed the type of lesion predicted from the various pretreatments with selective uptake blockers. These data suggest that changes in motor behavior in the adult rats, following neonatal 6-OHDA treatment, are specifically related to a DA-denervation, whereas an NA lesion does not seem to influence the spontaneous motor behavior. However, following the selective DA lesion, significant increases of serotonin levels in striatum and cerebellum were observed, while following selective NA lesions an increase of cerebellar NA levels was found concomitant with drastic reductions of NA levels in frontal cortex and spinal cord.

Aging↗

PubMed1989

Effects of d-amphetamine and methylphenidate on hyperactivity produced by neonatal 6-hydroxydopamine treatment.

Neonatal intracisternal administration of 6-hydroxydopamine (6-OHDA, 50 micrograms on day 1 after birth) caused a marked hyperactivity when the rats were tested as adults. These rats also showed severe DA depletions in striatum and nucleus accumbens. Pretreatment with the noradrenaline (NA) uptake inhibitor desipramine provided protection against NA depletion in frontal cortex and nucleus accumbens. Pretreatment with DA uptake inhibitors, amfolenic acid or GBR 12909, before 6-OHDA, provided full protection against DA depletion but produced marked NA depletion in frontal cortex. These rats did not demonstrate any degree of hyperactivity. Low doses of d-amphetamine (0.25 mg/kg SC) or methylphenidate (1 mg/kg SC) reversed the hyperactivity in DA-depleted rats but increased motor activity in vehicle-treated and NA-depleted rats. Higher doses of d-amphetamine (1 mg/kg) or methylphenidate (4 mg/kg) produced potentiated levels of locomotion but attenuated levels of rearing in DA-depleted animals. The results further suggest the utility of the neonatal DA lesion in rats as a potential animal model for derivation of therapeutic agents that may be efficacious in the treatment of the hyperkinetic syndrome.

Animals↗

PubMed1989

Behaviour in rats maintained by low differential reinforcement rate: effects of delta 1-tetrahydrocannabinol, cannabinol and cannabidiol, alone and in combination.

Rats were trained to respond according to a low rate differential reinforcement (DRL) 72 sec schedule of operant behaviour. The animals were then tested with delta 1-tetrahydrocannabinol (delta 1-THC), cannabinol, and cannabidiol alone and in combination. Tests with single doses of delta 1-THC (dose-range: 0.3-5.6 mg/kg) and cannabinol (dose-range: 1-56 mg/kg) but not cannabidiol (dose-range 3-100 mg/kg), yielded a dose-related biphasic effect on the response rate. Small doses of delta 1-THC and cannabinol increased the rate of responding, large doses of these agents decreased it. Cannabidiol alone only decreased the rate of responding (occurring at large doses). The rate of reinforcement generally was decreased when response rates increased and vice versa. Cannabidiol (10 and 30 kg/kg), together with delta 1-THC (1 and 3 mg/kg), decreased the response output and increased the rate of reinforcement. Similar results were observed with combinations of cannabinol (10 and 30 mg/kg) and cannabidiol (10 and 30 mg/kg). Combinations of delta 1-THC (0.3 and 1 mg/kg) and cannabinol (1 and 3 mg/kg) also reduced the response rate and there were no significant changes in the rate of reinforcement. Hence the actions of delta 1-THC and cannabinol on behaviour in rats maintained by low rate differential reinforcement were similar (approximate difference in potency 1:10), whereas no stimulation of response rate was demonstrated with cannabidiol. Vehicle and day of testing (Tuesday or Friday) variables were found not to affect the results.

Animals↗

PubMed1989

Serotonin and depression: old problems and new data.

1. Several lines of evidence implicating some dysfunction or alteration to brain serotonergic systems in depressive states are summarized. 2. Some aspects of the interactions between the 5-HT and catecholamine pathways in the action of antidepressant drugs are examined. 3. Finally, the important role of NA modulation of serotonergic activity in the action of antidepressants is suggested.

Animals↗

PubMed1989

Behavior of mother rats in conflict tests sensitive to antianxiety agents.

Previous studies of freezing and open-field activity have demonstrated that lactating rats are less fearful or less anxious than nonpregnant ones. The purpose of this investigation was to observe the behavior of mother rats in conflict tests, which are frequently used in studies on the neurobiology of anxiety. In the punished drinking test, in which licking from a water spout is punished by electric shocks, mothers (observed on Day 1 postpartum following 24 hr of water deprivation) were found to drink more than virgins. Mothers (Day 1 postpartum) also consumed more food than controls in an unfamiliar open field. In contrast, no difference between mothers (Day 5 postpartum) and virgins was present in the exploration of an electrified shock probe. The largest maternal anticonflict effects in the drinking and feeding tests were recorded when the females were tested with their pups. Increased punished drinking was also observed in virgin rats treated with the anxiolytic benzodiazepine midazolam. Water-deprived virgins and mothers did not differ in the shock titration test, a result suggesting that diminished pain reactivity was unlikely to account for the increased punished drinking in mothers. Moreover, females in late pregnancy, which are hypoalgesic (Gintzler, 1980), did not lick more than virgins in the punished drinking test. Following 24 hr of water deprivation, unpunished drinking was higher in lactating females than in virgins, so the increased acceptance of punishment by mothers might have been due to their being more thirsty than virgins.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1989

Adaptive changes in alpha-2 adrenoceptor mediated responses: analgesia, hypothermia and hypoactivity.

The acute effects of the alpha-2 adrenoceptor agonists, clonidine and guanfacine, upon antinociception, hypothermia and motor activity were compared under conditions of receptor antagonism, denervation, and chronic administration of a tricyclic antidepressant compound. The analgesic actions of clonidine and guanfacine were antagonised by idazoxan, an alpha-2 receptor antagonist, but potentiated by pretreatment with the noradrenaline neurotoxin DSP4, and attenuated by chronic treatment with desipramine (DMI). Clonidine- and guanfacine-induced hypothermia was antagonised by idazoxan, potentiated by prior treatment with DSP4 and attenuated by chronic administration with DMI. Both clonidine and guanfacine produced decreases in motor activity that were attenuated by idazoxan but unaffected by prior DSP-4 treatment. Chronic DMI administration also attenuated clonidine-induced hypoactivity but potentiated guanfacine-induced hypoactivity. These diverse results describe both similar and differential adaptive mechanisms modulating the functional effect of alpha-2 receptor systems in the central nervous system.

Adaptation, Physiological↗

PubMed1989

Ultrasound detection of axillary lymph node metastases in breast cancer.

Presence or absence of lymph node metastases is the most accurate prognostic indicator in breast cancer. Clinical examination is unreliable in detecting involved nodes. Preoperative ultrasound scan of the axilla has been performed in 140 consecutive women with breast cancer. The sensitivity for involved nodes was 66% which was significantly higher than clinical examination (42%) (P = less than 0.01). However ultrasound gave more false positives than clinical examination and thus no overall improvement in prognostic information was achieved.

Adult↗

PubMed1988

Galanin impairs acquisition but not retrieval of spatial memory in rats studied in the Morris swim maze.

The effect of intraventricular administration of the neuropeptide galanin on acquisition and retrieval in a modified Morris swim maze was studied in rats. Galanin induced a significant deficit in the acquisition of the task while no effects on the retrieval were observed. No deficits were seen 24 h after the last treatment. Galanin did not increase the number of failures to reach the platform. It is suggested that endogenous galanin modulates learning possibly via the galanin-containing cholinergic neurons in the septum-basal forebrain area projecting to the hippocampus and cortex.

Animals↗

PubMed1988

Evidence for crosstolerance to the analgesic effects between morphine and selective alpha 2-adrenoceptor agonists.

Rats were injected subcutaneously (s.c.) with morphine (5 mg/kg) until tolerance developed to its antinociceptive action, or with 0.9% saline which was used as vehicle for morphine. Subsequently, both groups of animals were given an intrathecal (i.th.) dose of either noradrenaline (2 micrograms), clonidine (12.5 micrograms) or guanfacine (12.5 micrograms), that had been found previously to be reliably antinociceptive. In the saline-treated animals, these doses of noradrenaline, clonidine or guanfacine induced clear antinociceptive effects, but not in the morphine-group. It is therefore concluded that cross-tolerance to the antinociceptive effects of systemic morphine and the alpha-adrenoceptor agonists was obtained. The cross-tolerance between morphine on one hand, and noradrenaline, clonidine and guanfacine on the other, implies that a substantial opiate-adrenoceptor interaction exists in antinociceptive processes.

Adrenergic alpha-Agonists↗

PubMed1988

Norepinephrine-stimulated inositol phospholipid breakdown in the rat cerebral cortex following serotoninergic lesion.

Norepinephrine (NE)-stimulated inositol phospholipid hydrolysis ("PI breakdown") in rat cerebral cortical miniprisms was used as a measure of alpha 1-adrenoceptor function following serotonin and/or NE depletion. The use of ascorbic acid to prevent autooxidation of the NE during the PI breakdown assay was found to be warranted. Treatment of rats with 5,7-dihydroxytryptamine and DSP4 produced selective depletions of serotonin (79-95%) and NE (69-85%), respectively, in cortical and hippocampal brain regions. The degree of cortical NE-stimulated PI breakdown in the lesioned animals was not significantly different from that in the control animals, suggesting that under the conditions used, serotonin and NE depletion do not lead to a changed sensitivity of alpha 1-adrenoceptors coupled to PI breakdown in the rat cortex.

5,7-Dihydroxytryptamine↗

PubMed1988

Intrathecal noradrenaline restores 5-methoxy-N,N-dimethyltryptamine induced antinociception abolished by intrathecal 6-hydroxydopamine.

Intrathecal administration of 6-hydroxydopamine (6-OHDA) abolished the antinociceptive effects of acute administration of 5-methoxy-N,N-dimethyltryptamine (5-MeODMT, 1 mg/kg, s.c.) in the hot-plate, tail-flick and shock titration tests of nociception. The antinociceptive effects of 5-MeODMT, abolished by the prior intrathecal 6-OHDA treatment, were restored by intrathecal administration (2 or 1 microgram) of noradrenaline (NA), immediately prior to 5-MeODMT, in all three tests of nociception. Biochemical analysis confirmed severe NA depletions (95 percent loss) in the lumbar and thoracic regions of the spinal and much lesser dopamine depletions (25-35 percent loss). Intrathecal 5,7-dihydroxytryptamine (5,7-DHT) attenuated 5-MeODMT induced antinociception in the tail-flick test and combined NA + 5-MeODMT induced antinociception in the hot-plate and tail-flick tests. Intrathecal administration of 5,7-DHT caused a severe depletion of 5-hydroxytryptamine in the lumbar region of the spinal cord. The present findings demonstrate further the modulatory role of NA upon serotonergic systems in nociception and indicate the necessity of NA availability for induction of 5-MeODMT analgesia.

5,7-Dihydroxytryptamine↗

PubMed1988

Neonatal 6-hydroxydopamine-induced dopamine depletions: motor activity and performance in maze learning.

Three experiments were performed to study the effect of dopamine (DA) depletions, induced by neonatal intracerebroventricular (ICV) treatment with 6-hydroxydopamine (6-OHDA), upon measures of spontaneous motor activity. Instrumental learning for food reward in an Olton radial arm maze and escape learning from a large, circular water maze were studied also. Motor activity was measured by direct observation of rats in a modified radial arm maze and by use of automated test cages equipped with photocell devices. 6-OHDA-treated rats demonstrated considerable and long-lasting locomotor (ambulation) activity and total activity increases. 6-OHDA-treated rats showed notably less rearing activity than the vehicle-treated rats during the initial 20 min of each 60-min test period. However, over the second half of these 60-min test periods, the 6-OHDA-treated rats demonstrated significantly more rearing activity than the vehicle-treated rats. In the acquisition of the running response, to obtain the 8 food pellets placed in each of the 8 arms of the radial arm maze, 6-OHDA rats showed a retarded acquisition, as measured by the latency and number of arms visited to acquire all eight pellets. 6-OHDA-treated rats failed completely to acquire the Morris-type swim maze task by which they were required to locate a platform just under the water surface in a circular water tank. The neurochemical assays indicated severe DA depletion in several forebrain regions. The present findings add to existing indications of the potential of this DA depletion condition as an animal model of the minimal brain dysfunction syndrome.

Animals↗

PubMed1988

Some aspects of stress and depression.

1. The role of stress in depressive illness is discussed together with utility of the "learned helplessness" model and some neuropharmacological correlates of uncontrollable shock. 2. Similarities and differences between chronic antidepressant treatment and chronic stress treatment regimes are reviewed. 3. Finally the role of adaptive process in stress on antidepressant treatments is discussed.

Animals↗

PubMed1988

Noradrenergic and serotonergic involvement in brief shock-induced analgesia in rats.

Four experiments were performed to investigate the effects of different techniques causing noradrenergic and serotonergic depletions in the brain and spinal cord on brief shock-induced analgesia. Newborn pups were administered N-2-choloroethyl-N-ethyl-2-bromobenzylamine systemically (2 x 50 mg/kg, ip) and 6-hydroxydopamine administered either systemically (100 micrograms/g, sc) or directly (8 micrograms in 1 microliter, bilaterally) into the locus coeruleus region, or intrathecally (20 micrograms in 10 microliter) into the lumbar subarachnoidal space, caused notable and consistent attenuations of the analgesia caused by brief shock. These treatments reduced noradrenaline concentrations in the spinal cord drastically. A potentiation of brief shock-induced analgesia was caused by the administration of p-chlorophenyl-alanine, whereas administration of 5,7-dihydroxytryptamine, into the nucleus raphe magnus or intrathecally into the subarachnoidal space, produced attenuation of the analgesic effect. Biochemical analyses revealed marked 5-hydroxytryptamine depletions in the spinal cord. The present findings are discussed with regard to the role of spinal noradrenaline and 5-hydroxytryptamine involvement in brief shock-induced analgesia and in reactions to stressful events.

Animals↗

PubMed1988

Acquisition and reversal of taste/tactile discrimination after forebrain noradrenaline depletion.

Two experiments were performed to assess the role of noradrenaline (NA) on the acquisition of an aversively motivated discrimination task and its reversal. A conditioned taste aversion procedure was used. The NA depletions were achieved through two different pharmacological means: systemic N-2-chloroethyl-N-ethyl-2-bromo-benzylamine (DSP4) and destruction of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine. Both procedures caused marked reductions of NA in the frontal cortex and hippocampus. In neither of the studies (Experiment 1, DSP4, and in Experiment 2, DNAB) were there any significant changes between controls and NA-depleted rats in either the rate of acquisition of the original discrimination (Phase 1) or the subsequent reversal (Phase 2). This occurred irrespective of which of the two stimuli (a taste cue, i.e., saccharin presented in bottles with nozzles that do not have ball bearings, "silent bottles," or a tongue-tactile cue, i.e., water in bottles with nozzles that had ball bearings "noisy bottles") initially was used as the conditioned stimulus (CS1, i.e., the stimulus first followed by contingent administration of lithium chloride, and later, in Phase 2, followed by saline injections). Thus NA does not appear to be critically involved in the acquisition and reversal of a taste/tactile discrimination task. The significance of forebrain NA for other discrimination tasks is discussed.

Animals↗

PubMed1988

Prenatal methylazoxymethanol treatment potentiates d-amphetamine- and methylphenidate-induced motor activity in male and female rats.

The effects of the stimulant drugs, d-amphetamine and methylphenidate, upon the motor activity of male and female off-spring of pregnant rats, treated on gestation day 15 with the antimitotic agent methylazoxymethanol (MAM, 25 mg/kg) were studied in four experiments. Cortical and striatal hypoplasia induced by prenatal administration of MAM resulted in increased concentrations of catecholamines in those regions. Administration of d-amphetamine and methylphenidate caused significant increases in motor activity; this effect was markedly potentiated in the MAM-treated rats, both the male and female off-spring. Thus, the locomotion and total activity parameters showed similar, but not identical, drastic increases in behaviour induced by the stimulant drugs as a result of the prenatal MAM treatment whereas for the rearing parameter a lesser potentiation by the MAM treatment was observed. This potentiation of the excitatory effects of the stimulant compounds upon the behavioural parameters is interpreted in terms of a relative increase in the density of catecholaminergic terminals in the forebrain regions of the central nervous system. The present results are discussed with regard to the utility of prenatal MAM treatment as a possible animal model for certain neurological disorders.

Animals↗