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T Archer

Publications and source records attributed to T Archer.

At least 109 records · Page 6Linked to original sources
PubMed1986

Noradrenaline-stimulated inositol phospholipid breakdown as a measure of alpha 1-adrenoceptor function in rat hippocampal miniprisms after repeated antidepressant treatment.

Noradrenaline-stimulated inositol phospholipid (PI) breakdown in rat hippocampal miniprisms was used as a measure of alpha 1-adrenoceptor function after repeated antidepressant treatment. After 24-29 days of oral treatment with either desipramine, mianserin, maprotiline or zimeldine (all at doses of 10 mg/kg b.i.d.), there was no significant difference in the degree of stimulation of hippocampal PI breakdown by 0.4, 2, 10 or 100 microM noradrenaline. It is concluded that there is no supersensitivity of hippocampal alpha 1-adrenoceptors coupled to PI breakdown after repeated antidepressant treatment under the conditions used.

Animals↗
PubMed1986

5-HT agonist induced analgesia modulated by central but not peripheral noradrenaline depletion in rats.

The antinociceptive effect elicited by the 5-hydroxytryptamine (5-HT) agonist 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) was reversed or blocked in animals which had previously sustained severe spinal noradrenaline (NA) depletion via either systemic N-2-chlorethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP 4), neonatal 6-hydroxydopamine (neon. 6-OHDA), or intrathecal 6-OHDA treatment. Biochemical analysis of the lumbar spinal cord samples confirmed severe central NA depletions. Animals were tested with nondamaging heat pain (tail-flick test, hot-plate test) and electric footshock titration to determine the amount of antinociception or nociception. Peripheral NA depletion following intravenous (i.v.) 6-OHDA injection to adult rats had no effect on the antinociception induced by 5-MeODMT, but did cause severe NA depletions in the left heart atrium. These results suggest a modulatory effect of central and not peripheral noradrenergic system upon 5-HT agonist induced analgesia, and also give evidence that this effect is spinally mediated.

5,7-Dihydroxytryptamine↗
PubMed1986

Noradrenaline and the context-dependent extinction effect.

Three experiments were performed to examine the effects of noradrenaline (NA) depletion upon the context-dependent extinction effects in conditioned taste-aversion learning. Three different methods were used to deplete NA: lesions of the dorsal noradrenergic bundle (DNAB) with 6-hydroxydopamine (6-OHDA), lesions induced by neonatal treatment with 6-OHDA and lesions induced by systemic administration with the NA neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). In each experiment, novel saccharin was presented in novel noisy bottle followed by lithium chloride. Later, during the extinction phase, half the control and half the NA depleted rats received saccharin in noisy bottles while the other half received saccharin in silent bottles. In the control condition, the rats that received saccharin in the noisy bottles (same context as conditioning) showed considerably more aversion than those that received saccharin in the silent bottles (different context to conditioning); NA depletion attenuated this effect. Reinstatement of the conditioning context (noisy bottle) resulted in a stronger aversion in the case where the different context (silent bottle) was present during extinction; this effect was attenuated in the NA depletion condition. These findings maintain a role for noradrenaline in compound conditioning tasks.

Animals↗
PubMed1986

Impaired selective attention in methylazoxymethanol-induced microencephalic rats.

Prenatal treatment of rats on gestation day 15 with methylazoxymethanol (MAM) caused forebrain microencephaly. Several behavioral tests were performed when the rats had reached an adult age. MAM treated rats were hyperactive, and were severely impaired in the acquisition of successive position reversal in a T-maze. The microencephalic rats failed also to demonstrate contextual control of latent inhibition (the stimulus preexposure effect) in taste-aversion conditioning. These results indicate that MAM treatment disrupts attentional processes and that this may account for the learning impairment.

Animals↗
PubMed1986

Role of central noradrenaline neurons in the contextual control of latent inhibition in taste aversion learning.

Three experiments were performed to examine the effects of noradrenaline (NA) depletion, using 3 different methods: lesions of the dorsal noradrenergic bundle (DB) with 6-hydroxydopamine (6-OHDA), lesions induced by neonatal treatment with 6-OHDA and lesions induced by systemic DSP4 upon latent inhibition, using the taste-aversion learning procedure. NA depleted and control (sham, vehicle or saline) rats were given pre-exposure trials to either novel saccharin or to novel saccharin in a novel type of drinking bottle (the noisy bottle). Later, during conditioning trials saccharin was presented in the noisy bottles for all the rats, followed by lithium chloride injections. Saccharin aversions, tested for in the noisy bottles, indicated considerably weaker saccharin aversions (i.e. more latent inhibition) by the control groups pre-exposed to both saccharin and the noisy bottles. These context-dependent latent inhibition effects were clearly attenuated by all 3 treatments that depleted central NA. Biochemical assays confirmed the NA depletions in each case. The results, demonstrating the intimate role of central NA neurons in contextual control of latent inhibition in taste-aversion learning, appear to conform with current attentional theories of NA function in the forebrain.

Animals↗
PubMed1986

Attenuation of sensory preconditioning by noradrenaline depletion in the rat.

In order to investigate the effect of noradrenaline (NA) depletion upon an associative learning phenomenon, sensory preconditioning, rats were inflicted with either 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle (DNAB) or the locus coeruleus (LC), or with systemic injections of the NA neurotoxin, N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4). Using appropriate controls (the UP groups) sensory preconditioning was demonstrated clearly in the non-lesion conditions (Sham or saline), but was blocked or strongly attenuated in the DNAB and DSP4 conditions. LC lesions did not affect sensory preconditioning. These findings suggest that the loss of central NA may cause some disruption of some aspects of complex associative learning. The role of NA in sensory preconditioning may be relevant to current notions of NA function.

Animals↗
PubMed1986

Selective attention and place navigation in rats treated prenatally with methylazoxymethanol.

Prenatal treatment of rats on gestation day 15 with methylazoxymethanol (MAM) caused forebrain microencephaly. The behavioral analyses included measures of spontaneous motor activity and tests for cognitive deficits, and were performed when the rats had reached adult age. Female MAM-treated rats failed to demonstrate contextual control of latent inhibition, which confirms earlier findings with male rats. Male MAM-treated rats demonstrated a notable impairment of place navigation in a swim-maze, but showed as strong sensory preconditioning as the control animals. Biochemical analyses indicated considerable increases in catecholamine levels in the cerebral cortex, hippocampus and striatum. The cognitive deficits, characterised by the various conditioning (taste-aversion) and instrumental learning (swim-maze) tasks, suggested that the MAM rats are deficient in their capacity to attend selectively to the relevant stimulus in complex arrangements of the stimulus situation.

Abnormalities, Drug-Induced↗
PubMed1986

Spinal and locus coeruleus noradrenergic lesions abolish the analgesic effects of 5-methoxy-N,N-dimethyltryptamine.

Two experiments were performed on Sprague-Dawley rats to study the effects of noradrenaline and 5-hydroxytryptamine depletion upon the antinociceptive effects of acute 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) administration. 6-Hydroxydopamine-induced lesions following microinjections to either the locus coeruleus or the spinal cord (lumbar) abolished completely 5-MeODMT-induced analgesia in the tail-flick, hot-plate, and shock titration tests whereas 5,7-dihydroxytryptamine-induced lesions of the nucleus raphe magnus and the lumbar spinal cord attenuated 5-MeODMT analgesia in the tail-flick and shock titration tests. Thus, the experiments serve to demonstrate an important interaction between descending noradrenergic and serotonergic pathways, possibly at a spinal locus.

Analgesics↗
PubMed1986

Noradrenaline and sensory preconditioning in the rat.

Two experiments were performed to investigate the effect of noradrenaline (NA) depletion following systemic administration of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4; 50 mg/kg, ip) on sensory preconditioning in the rat. For sensory preconditioning, a taste (saccharin, CS2) and a special type of drinking bottle (noisy bottle) were paired during Phase 1. During Phase 2, the noisy bottle (CS1) was paired with lithium chloride, and, finally, during Phase 3 the aversion to saccharin (CS2) was tested for in saccharin preference tests. The DSP4 treatment disrupted rats' ability to form sensory preconditioning, and this effect could not be explained on the basis of enhanced neophobia, stimulus generalization, or a deficit in first-order conditioning in DSP4-treated rats. These findings are closely related to these and other issues of associative learning such as contextual control of latent inhibition and extinction. The evidence from the present data suggests that NA-depleted rats fail to form associations between the CS1 and CS2 during sensory preconditioning and, as such, are consistent with other data from various compound conditioning experiments on the functional role of NA in learning and memory.

Animals↗
PubMed1986

5-Methoxy-N,N-dimethyltryptamine-induced analgesia is blocked by alpha-adrenoceptor antagonists in rats.

The effects of the alpha-adrenoceptor antagonists prazosin, phentolamine and yohimbine upon 5-methoxy-N,N-dimethyltryptamine (5-MeODMT)-induced analgesia were tested in the hot-plate, tail-flick and shock-titration tests of nociception with rats. Intrathecally injected yohimbine and phentolamine blocked or attenuated the analgesia produced by systemic administration of 5-MeODMT in all three nociceptive tests. Intrathecally administered prazosin attenuated the analgesic effects of 5-MeODMT in the hot-plate and tail-flick tests, but not in the shock titration test. Intrathecal yohimbine showed a dose-related lowering of pain thresholds in saline and 5-MeODMT-treated animals. Phentolamine and prazosin produced normal dose-related curves in the hot-plate test and biphasic effects in the shock titration and tail-flick tests. These results demonstrate a functional interaction between alpha 2-adrenoceptors and 5-HT agonist-induced analgesia at a spinal level in rats.

Adrenergic alpha-Antagonists↗
PubMed1986

Chronic treatment with antidepressant drugs and the analgesia induced by 5-methoxy-N,N-dimethyltryptamine: attenuation by desipramine.

The effect of chronic and acute oral or intraperitoneal treatment with the antidepressant drugs, desipramine, amitriptyline, alaproclate and iprindole, upon pain thresholds in the tail flick, hot plate and shock titration tests of nociception in saline- and 5-MeODMT-treated rats was studied. Chronic desipramine treatment increased the pre-test tail flick latencies. In the saline-treated rats, chronic oral desipramine treatment increased tail flick latencies, whereas chronic oral amitriptyline treatment decreased tail flick latencies. In 5-MeODMT-treated rats, chronic oral desipramine treatment attenuated the effects of 5-MeODMT (1 mg/kg) in all three tests of nociception, whereas chronic amitriptyline caused a potentiation in the tail flick and hot plate tests. Chronic oral iprindole treatment attenuated 5-MeODMT-induced analgesia in the hot plate test. Chronic intraperitoneal desipramine treatment attenuated 5-MeODMT analgesia in the tail flick and shock titration tests. In a different chronic treatment experiment, oral desipramine treatment attenuated 5-MeODMT analgesia in the tail flick test and zimeldine did for both the tail flick and hot plate tests, whereas mianserin potentiated 5-MeODMT-induced analgesia in both the tail flick and hot plate tests. In the saline-treated rats, acute treatment with all four drugs, desipramine, amitriptyline, iprindole and alaproclate, elevated the shock thresholds, whereas in 5-MeODMT-treated rats, desipramine and amitriptyline elevated shock thresholds. Two main conclusions can be drawn: chronic desipramine caused a quite consistent attenuation of 5-MeODMT-induced analgesia and the effects of acute treatment differed strongly from that of the chronic treatment. The effects of chronic administration with these antidepressants were compared with other findings using different measures of behavioural and receptor function.

Analgesics↗
PubMed1985

The hindlimb extension reflex is not a reliable marker of post-decapitation convulsions or spinal noradrenaline depletion in rats.

The degree of hindlimb extension reflex (ER), post-decapitation reflex (PDR) and noradrenaline (NA) depletion was measured under various treatment regimens involving the neurotoxins DSP4 and 6-OHDA. Neither neonatal 6-OHDA treatment, direct application of 6-OHDA to the locus coeruleus nor DSP4 treatment produced a blockade of ER that could be associated with the loss of PDR and the spinal NA depletion, whereas intrathecal 6-OHDA treatment caused a strong loss of both ER and PDR related to severe spinal NA depletion. No correlation was obtained between the ER and PDR in a large number of DSP4-treated rats.

Animals↗
PubMed1985

Noradrenaline depletion increases noradrenaline-induced antinociception in mice.

Mice were treated with N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4), which causes severe noradrenaline (NA) depletions in brain regions and the spinal cord, or vehicle i.p. They were tested 14 days later for antinociception induced by intrathecal injections of different doses of NA. A potentiation of the NA effect upon pain sensitivity was observed, with both an increase in the magnitude and duration of the antinociceptive responses. Upon biochemical analysis of spinal cords, it was found that DSP4-treated mice had a 80% depletion of NA, whereas dopamine and 5-hydroxytryptamine were unaffected. Radioligand binding of [3H]clonidine in membranes prepared from spinal cord, showed no differences in density of alpha 2-adrenoceptors, but the affinity had been increased, probably explaining the supersensitivity.

Animals↗
PubMed1985

Blockade and reversal of 5-methoxy-N,N-dimethyltryptamine-induced analgesia following noradrenaline depletion.

The acute effects of the 5-hydroxytryptamine agonist, 5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), upon pain sensitivity, using shock titration, tail-flick and hot-plate methods, in noradrenaline- and 5-hydroxytryptamine-depleted rats were examined. Noradrenaline depletion, following the systemic administration of N-2-chloroethyl-N-ethyl-2-bromobenzylamine hydrochloride (DSP4, 2 X 50 mg/kg, i.p.), caused a reversal of the analgesic effect of 5-MeO-DMT on shock-titration from hypo- to hypersensitivity, and a total blockade of the antinociceptive effect of 5-MeO-DMT upon pain responses in the hot-plate and tail-flick tests. Pretreatment with either p-chloroamphetamine (2 X 10 mg/kg) or p-chlorophenylalanine (200, 100, 100 mg/kg), that depletes central 5-hydroxytryptamine stores, failed to alter the analgesia caused by acute 5-MeO-DMT. Strong evidence is provided for the effect of central noradrenaline depletion upon the analgesic effect of the 5-HT agonist. These findings suggest an important tonic influence of the noradrenaline system upon the descending spinal 5-HT pathway in rats.

Analgesics↗
PubMed1985

Blockade of intrathecal 5-hydroxytryptamine-induced antinociception in rats by noradrenaline depletion.

The analgesic effect of 5-hydroxytryptamine (5-HT, 200 and 250 micrograms/kg) administered into the lumbar intrathecal space of rats was blocked in the tail-flick, hot-plate and shock titration tests of nociception when the animals had previously been treated with N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4), which depletes noradrenaline in the spinal cord. These results suggest an important modulatory role of noradrenaline upon spinal 5-HT mechanisms.

Analgesics↗
PubMed1985

Active and passive avoidance following the administration of systemic DSP4, xylamine, or p-chloroamphetamine.

Groups of rats were administered either DSP4 (50 mg/kg, ip), xylamine (50 mg/kg, ip), or p-chloroamphetamine (2 X 10 mg/kg, ip), either 2 weeks or 1 week before the testing of two-way active avoidance. DSP4 and xylamine, the selective noradrenaline (NA) neurotoxins, caused a two-way avoidance impairment but p-chloroamphetamine, the selective 5-hydroxytryptamine (5-HT) neurotoxin, did not do so. Pretreatment with desipramine (20 mg/kg, ip) blocked the avoidance impairment caused by DSP4 and xylamine treatment. Neither DSP4 nor xylamine caused any alteration of passive avoidance retention. The biochemical analyses indicated severe NA, but not 5-HT, depletions in the DSP4 and xylamine conditions and drastic 5-HT, but not NA, depletions in the p-chloroamphetamine conditions. These results confirm and extend earlier findings concerning the role of NA in avoidance behavior.

Amphetamines↗