The effect of stimulus preexposure upon the context effect in taste-aversion learning in noradrenaline-depleted rats.
Explore the source record for details and available documents.
Animals↗
Biomedical subjects
T Archer
Publications and source records attributed to T Archer.
Increased total activity in the rat after L-tryptophan plus the monoamine oxidase-A inhibitor amiflamine but not after L-tryptophan plus clorgyline.
The effect of pretreatment with either saline or the monoamine oxidase-A inhibitors clorgyline and amiflamine upon the total activity, locomotion and rearing behaviour of the rat induced by various doses of the monoamine precursor L-tryptophan was studied by use of automated activity boxes. Amiflamine (2.5 and 5.0 mg kg-1, i.p.) increased in a dose-dependent manner total activity and to a lesser extent, locomotion when given 60 min before L-tryptophan (100 mg kg-1, i.p.). The increased activity was seen after amiflamine plus either 25 or 75 mg kg-1 L-tryptophan. Rearing behaviour was not affected. Analysis of 5-hydroxytryptamine (5-HT) and its deaminated metabolite 5-hydroxyindoleacetic acid (5-HIAA) by high performance liquid chromatography with electrochemical detection indicated that in both frontal cortex and hypothalamus, amiflamine (at both doses) increased 5-HT and reduced 5-HIAA concentrations. Combination of amiflamine with L-tryptophan (100 mg kg-1, i.p.) resulted in a higher 5-HT concentration being found than after amiflamine alone. L-Tryptophan treatment alone did not change 5-HT concentrations but increased 5-HIAA concentrations. Clorgyline, at a dose of either 1 or 5 mg kg-1 i.p. plus L-tryptophan (25 or 100 mg kg-1, i.p.) did not increase total activity, locomotion or behaviour. A number of possible explanations for the differences in the behavioural effects of clorgyline and amiflamine when given with L-tryptophan are discussed. It is concluded that in addition to monoamine oxidase-A inhibition, other pharmacological effects of the drugs, such as 5-HT release (amiflamine) and inhibition of tryptophan hydroxylation (clorgyline) may be of importance in determining the magnitude of the increase in activity when the compounds are given together with L-tryptophan.
Animals↗
Complete blockade and attenuation of 5-hydroxytryptamine induced analgesia following NA depletion in rats and mice.
The effect of pretreatment with the noradrenaline neurotoxin, N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), upon the analgesia induced by various doses of 5-hydroxytryptamine (5-HT) was examined in rats and mice. DSP4 treatment (2 X 50 mg/kg, intraperitoneally) of rats caused a complete blockade of 5-HT induced analgesia in the tail-flick, hot-plate and shock titration tests. DSP4 treatment (1 X 50 mg/kg, intraperitoneally) of mice caused a partial blockade of 5-HT induced analgesia in the hot-plate test, but no significant blockade in the tail-flick test. These results are discussed with regard to serotonergic-noradrenergic interactions and the species discrepancy in nociceptive testing.
Analgesics↗
Antagonism of 5-methoxy-N,N-dimethyltryptamine-induced changes in postdecapitation convulsions in rats by repeated treatment with drugs enhancing 5-hydroxytryptamine neurotransmission.
Repeated administration of drugs that increase tryptaminergic neurotransmission antagonized the increase in latency to onset and the duration of postdecapitation convulsions (PDCs) induced by an acute 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) injection; Zimelidine (2 X 5 mg kg-1), fluoxetine (2 X 5 mg kg-1), amiflamine (2 X 2.5 mg kg-1) and alpha-ethyltryptamine (2 X 2.5 mg kg-1) administered orally over 10 days caused a substantial blockade of the increase in latency to onset and duration of PDCs following 5-MeODMT, whereas alaproclate (2 X 5 mg kg-1), clorgyline (1 X 1 mg kg-1) and pargyline (2 X 2.5 mg kg-1) caused a lesser blockade. Repeated 5-MeODMT (3 X 2 mg kg-1) administration blocked the acute effects of 5-MeODMT (2 and 4 mg kg-1) upon PDCs completely. These findings indicate down-regulation of the 5-hydroxytryptamine receptors which mediate the action of 5-MeODMT on the PDCs and offer a simple model system for studying 5-HT receptor sensitivity changes at the spinal level.
Animals↗
Retention deficits induced by acute p-chloroamphetamine following fear conditioning in the rat.
Rats were given four inescapable shocks (1.0 mA) when confined to the right-hand corner of a modified shuttlebox. p-Chloroamphetamine (PCA) injected just before the retention test 24 h later completely blocked the immobile posture that was observed after saline injections. This retention deficit was shown to be selectively associated with 5-hydroxytryptamine (5-HT) release, since the administration of the 5-HT uptake inhibitors zimelidine and citalopram 60 min prior to PCA antagonized this effect. The 5-HT specificity of the deficit was further established by the findings that 5-HT-depleted rats (PCA, 2 x 10 mg/kg, and fenfluramine, 2 x 25 mg/kg), but not NA-depleted rats (DSP4, 1 x 50 mg/kg), or rats treated with zimelidine (2 x 20 mg/kg) 60 min before PCA (2 x 10 mg/kg), showed an almost complete blockade of the retention failure. The data presented may provide a useful experimental model for investigating the efficacy of functional 5-HT activity in the treatment of phobic anxiety.
Amphetamines↗
The effect of acute zimeldine and alaproclate administration on the acquisition of two-way active avoidance: comparison with other antidepressant agents, test of selectivity and sub-chronic studies.
The dose-dependent effect of acute zimeldine and alaproclate treatment upon the acquisition of two-way and one-way active avoidance in the rat was studied in a single-session and in a repeated-sessions design. Zimeldine (5-20 mg/kg, IP), but not alaproclate, caused disruptions of two-way avoidance acquisition. Acquisition deficits were also caused by citalopram and fluoxetine but not the other antidepressant drugs tested. Zimeldine, but not alaproclate or desipramine, caused a slight but non-significant impairment of one-way active avoidance; neither zimeldine nor alaproclate produced any effects upon fear conditioning and retention testing. The long-term action of p-chloroamphetamine (2 X 10 mg/kg) antagonised the acute zimeldine effect totally, and chronic treatment with zimeldine (15 days, 1 X 50 mumol/kg) and chlorimipramine (15 days, 2 X 10 mumol/kg) also caused some partial blockade of the two-way avoidance deficit. These data seem to suggest some involvement of serotonin (5-HT) in the observed disruptions of two-way active avoidance caused by acute zimeldine treatment.
Alanine↗
Effects of (-)3-PPP on acquisition and retention of a conditioned avoidance response in the rat.
The administration of (-)3-(3-hydroxyphenyl)-N-n-propylpiperidine (3-PPP) was found to partially, but significantly, suppress the acquisition (4-8 mg/kg IP) and performance (8-16 mg/kg IP) of a conditioned avoidance response (CAR) in male Sprague-Dawley rats. All statistically significant effects were observed within 2 h of injection. Furthermore, using a situation in which the CAR was dependent on a visual successive discrimination, it was shown that discriminative performance was unaffected, and that (-)3-PPP (12.5-25 mg/kg IP) but not (+)3-PPP, suppressed the CAR. When (-)3-PPP (6.25 mg/kg IP) was combined with haloperidol (0.1-0.4 mg/kg IP), additive effects on the CAR performance were observed. Considering these effects, and the doses of (-)3-PPP required to suppress the CAR performance, it is concluded that the effects obtained in the present experiments are primarily due to a blockade of postsynaptic DA receptors.
Animals↗
Role of olfactory bulbectomy and DSP4 treatment in avoidance learning in the rat.
Olfactory bulbectomized rats and DSP4-treated rats were studied on a two-way active avoidance task as well as on step-down passive avoidance and fear conditioning and retention tasks in three experiments. The DSP4-treated, but not olfactory bulbectomized, rats were impaired in acquiring two-way avoidance; bulbectomized, but not DSP4-treated, rats were found to show notable passive avoidance and fear retention deficits. Bulbectomized rats treated with DSP4 did not show passive avoidance and fear retention deficits, nor did these animals evidence the two-way avoidance impairment of the DSP4-treated rats. No alteration of dopamine-beta-hydroxylase activity in the frontal cortex and hippocampus as a result of the bulbectomy operation was indicated. The double dissociation between bulbectomized and DSP4-treated rats is discussed in terms of opponent behavioral processes, influenced by olfactory bulbectomy and DSP4, which may permit insights into experimental investigations of stress, anxiety, and depression.
Amines↗
Noradrenaline loss and the disruption of between-CS stimulus generalisation effects in aversion learning.
Explore the source record for details and available documents.
Animals↗
Active and passive avoidance performances following bilateral olfactory bulbectomy.
Explore the source record for details and available documents.
Animals↗
The importance of contextual elements in taste-aversion learning.
Explore the source record for details and available documents.
Animals↗
A parametric study of the effects of the noradrenaline neurotoxin DSP4 on avoidance acquisition and noradrenaline neurones in the CNS of the rat.
The effects of various doses of DSP4 on two-way active avoidance acquisition in rats and on central noradrenaline neurones were compared. Doses of DSP4 from 3 mg kg-1 i.p. and upwards injected one week before the onset of the avoidance trials significantly impaired two-way avoidance learning. The learning impairment caused by DSP4 (50 mg kg-1 i.p.) lasted for at least 10 weeks. Desipramine (20 mg kg-1) injected either 30 or 60 min before DSP4 (50 mg kg-1) antagonized the active avoidance impairment. A high dose of DSP4 (50 mg kg-1 i.p.) produced profound decreases in dopamine-beta-hydroxylase activity in the frontal cortex and in the concentrations of noradrenaline in various brain regions indicating degeneration of the locus coeruleus noradrenaline system. Low doses of DSP4 (3 and 6 mg kg-1 i.p.) produced small but significant decrease in the concentrations of noradrenaline (NA) in some regions, e.g. cerebral cortex, hippocampus, olfactory bulb and spinal cord. The avoidance impairment caused by the low dose of DSP4 (3 mg kg-1) was absent when rats were tested 10 weeks after treatment nor was NA depletion present when NA was analysed 3 months after treatment.
Amines↗
Attenuation of the post-decapitation convulsions after repeated treatment of rats with desipramine, imipramine and maprotiline.
The effects of repeated treatment of rats with the antidepressant or potential antidepressant agents alaproclate, citalopram, clomipramine, desipramine, imipramine, maprotiline, mianserin and zimeldine on the convulsions released by decapitation were examined. The noradrenaline uptake inhibitors desipramine, imipramine and maprotiline increased significantly the latency of onset of the post-decapitation convulsions (PDC's) after repeated administration of 10 mumol/kg orally twice daily, or 66 mumol/kg orally once daily (desipramine), for 15 days. The duration of the PDC's was slightly prolonged by these agents. A single acute dose of desipramine (20 mg/kg) administered at various time intervals before decapitation (1 to 24 hours) had no effect on the PDC's nor did repeated treatment with the other compounds examined, alaproclate, citalopram, clomipramine, mianserin and zimeldine, have any effect upon the PDC latency. The results are interpreted as evidence for noradrenaline receptor subsensitivity following chronic treatment.
Alanine↗
Effects of acute administration of 5-methoxy-N,N-dimethyltryptamine upon the latency and duration of post-decapitation convulsions.
The effect of acute administration of rats with the 5-hydroxytryptamine (5-HT) agonist drug 5-methoxy-N,N-dimethyltryptamine on the convulsions released by decapitation was examined. The postsynaptic agonist, 5-methoxy-N,N-dimethyltryptamine, prolonged the latency and duration from the 0.5 mg/kg dose upwards. Methergoline, 2.0 mg/kg intraperitoneally injected immediately prior to 5-methoxy-N,N-dimethyltryptamine, caused some considerable blockade of the effects of the 5-HT agonist on post-decapitation convulsions (PDG's). Long-term p-chloroamphetamine (2x10 mg/kg) and p-chlorophenylalanine (1 x 300 mg/kg) did not antagonise the 5-methoxy-N-N-dimethyltryptamine induced changes of PDC's but, by themselves, prolonged PDC duration. The utility of the 5-methoxy-N,N-dimethyltryptamine-PDC method for studying 5-HT receptor mechanisms may be worth considering.
Animals↗
Changes in serum ferritin and other 'acute phase' proteins following major surgery.
We have measured ferritin concentrations in healthy women, and ferritin, C-reactive protein, iron and total iron-binding capacity in patients undergoing hysterectomy or major gastrointestinal surgery. Pre-operative serum ferritin concentrations in patients awaiting hysterectomy were significantly lower than those for patients awaiting gastrointestinal surgery and also lower than those for healthy women of similar age. Healthy women aged between 51 and 60 years had significantly higher ferritin levels than women aged 35-50 years. All patients studied showed large increases in serum ferritin and C-reactive protein concentrations after surgery and approximately similar decreases in iron and in total iron-binding capacity.
Acute-Phase Proteins↗
Evidence for a selective brain noradrenergic involvement in the locomotor stimulant effects of amphetamine in the rat.
Male rats received the noradrenaline neurotoxin DSP4 (50 mg/kg) 7 days prior to injection of D-amphetamine (10 or 40 mumol/kg i.p.). The hyperactivity induced by D-amphetamine (10 mumol/kg) was significantly reduced by DSP4 pretreatment. However, the increased rearings and the amphetamine-induced stereotypies were not blocked by pretreatment with DSP4. The reduction of amphetamine hyperactivity induced by DSP4 was blocked by pretreatment with the noradrenaline-uptake blocking agent, desipramine, which prevents the neurotoxic action of DSP4. The present results suggest a selective involvement of central noradrenergic neurones in the locomotor stimulant effect of amphetamine in the rat.
Animals↗
T-maze learning, spontaneous activity and food intake recovery following systemic administration of the noradrenaline neurotoxin, DSP4.
Following systemic administration of the noradrenaline (NA) neurotoxin, DSP4 (50 mg/kg), rats were found to be retarded in the rate at which they acquired the "right-turn" running response in a modified T-maze choice situation, as measured by the total number of errors per session and median latency to reach the goal box. Desipramine (DMI, 20 mg/kg), injected 30 min before DSP4 blocked the acquisition retardation. DSP4 was found to have a short-lasting effect upon spontaneous motor activity, while food and water intake recovery was complete within 7 days of the injection. Both the NA-accumulation data and endogenous NA concentrations indicated profound NA, but not 5-hydroxytryptamine (5-HT) and dopamine (DA), depletions in the cortex, hippocampus and cerebellum. These data seem to confirm the role of the locus coeruleus-noradrenaline (LC-NA) system in an instrumental learning situation.
Amines↗
Latent inhibition following systemic DSP4: effects due to presence and absence of contextual cues in taste-aversion learning.
Three taste-aversion experiments were performed to test the effect of noradrenaline (NA) depletion, following systemic administration of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4), upon the Lubow "latent inhibition" effect in rats. DSP4-treated rats did not demonstrate any attenuation of latent inhibition, the conditioned stimulus (CS) preexposure effect. Instead, when the contextual conditions (provided by a noise-producing bottle) were so arranged that there was a "mismatch" from the saccharin preexposure to the saccharin-aversion conditioning phase, the DSP4 rats showed some considerable enhancement of latent inhibition. This disruption of the contextual control of the degree of latent inhibition evinced by the NA-depleted rats was found to bear a striking resemblance to the attenuated contextual control of extinction in taste aversion by DSP4 treated rats demonstrated earlier. Biochemical analysis of noradrenaline and serotonin accumulation performed after Experiment 1, and postdecapitation reflex analysis after each experiment, confirmed the selective NA depletion. These results are compared to earlier findings concerning noradrenaline and latent inhibition and the effects are discussed with reference to selective attentional and retrieval-based models of noradrenaline function in learning and memory.
Amines↗