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Biomedical subjects

T Archer

Publications and source records attributed to T Archer.

At least 145 records · Page 8Linked to original sources
PubMed1982

Serotonin involvement in aversive conditioning: reversal of the fear retention deficit by long-term p-chloroamphetamine but not p-chlorophenylalanine.

5-Methoxy-N,N-dimethyltryptamine (5-MeO-DMT), a serotonin (5-HT) agonist, fenfluramine and p-chloroamphetamine (PCA), which are 5-HT releasers, produce deficits in fear retention as indicated by a notable lack of the immobility resulting from inescapable shocks. Depletion of central 5-HT neurones after long-term PCA treatment (2 X 10 mg/kg) completely blocked the retention impairment resulting from acute PCA (2.5 mg/kg) and fenfluramine (5 mg/kg), and partially blocked the deficit produced by 5-MeO-DMT (4 mg/kg). 5-HT depletion after p-chlorophenylalanine (PCPA) treatment (200, 100, 100 mg/kg, 72, 48 and 24 h before) did not do so; this is in agreement with other findings which suggest the involvement of different 5-HT stores in the action of PCA and PCPA. These data further underline the importance of the ascending 5-HT pathway in aversive conditioning in the rat.

Amphetamines↗
PubMed1982

DSP4-induced two-way active avoidance impairment in rats: involvement of central and not peripheral noradrenaline depletion.

N-2-chloroethyl-N-ethyl-2-bromobenzylamine (DSP4) (50 mg/kg IP), a new selective noradrenaline (NA) neurotoxin, was found to cause a severe impairment of the acquisition of a two-way active avoidance task 1 week following administration, an effect that was blocked by the selective NA uptake inhibitor desipramine. In a second experiment, systemically injected 6-OHDA (2 x 30 mg/kg IP) was not found to cause any avoidance impairment, although its effects upon peripheral NA were still evident 21 days after administration: The peripheral NA depletion caused by DSP4 almost disappeared 14 days after injection. In a third experiment, the avoidance impairment induced by DSP4 was produced even 10 weeks after treatment. Data from both the shuttlebox experiment and an activity box experiment suggest that the acquisition impairment is not readily explained on the basis of some deficit in spontaneous behavior or an altered perception of pain. The present data suggest that the effect of DSP4 upon active avoidance acquisition is mediated via central, and not peripheral NA neurons.

Amines↗
PubMed1982

DSP4 (N-2-chloroethyl-N-ethyl-2-bromobenzylamine), a new noradrenaline neurotoxin, and stimulus conditions affecting acquisition of two-way active avoidance.

Several stimulus (conditioned stimulus [CS] and unconditioned stimulus) variables known to affect the rate of acquisition of the two-way active avoidance task were investigated in rats treated with the novel selective noradrenaline neurotoxin DSP4 (50 mg/kg, ip). Although the DSP4 rats did not demonstrate the linear relation between CS duration and avoidance acquisition to the same extent as the control rats, their avoidance performance was as drastically disrupted as that of the controls both by preexposure to the CS and by increasing levels of shock intensity. The DSP4 rats also evidenced fear retention for the shuttle box cues previously associated with inescapable shocks to as marked a degree as control rats. Biochemical data indicated profound noradrenaline depletion in the cortex and hippocampus and a lesser depletion in the hypothalamus. It seems unlikely that the small serotonin depletions evidenced here can account for the avoidance deficits. The present findings offer a behavioral characterization of the consistent DSP4-induced impairment of two-way active avoidance acquisition.

Amines↗
PubMed1982

Serotonin and fear retention in the rat.

p-Chloroamphetamine (PCA), which releases serotonin (5-HT) stores in brain regions, injected (5 mg/kg, ip) into male rats 40 min prior to the presentation of four inescapable shocks (.065 W) in the right-hand compartment of a normal shuttle box resulted in a profound fear-retention deficit as characterized by the total loss of the freezing and immobility posture that is normally the aftermath of shock presentation; zimelidine (10 mg/kg) 60 min before PCA completely blocked the disruption of fear. The "PCA effect" on fear retention was found at the 2.5 mg/kg but not quite at the 1.25 mg/kg dose, and when PCA (5 mg/kg) had been injected at least 8 hr before conditioning. The selective 5-HT uptake inhibitors zimelidine and fluoxetine, but not the noradrenaline (NA) uptake inhibitor desipramine, blocked the PCA effect, as did the 5-HT antagonist methergoline, but not the selective dopamine antagonist pimozide. A total retention impairment with a conditioning-testing delay of just 60 min was also evidenced, and the administration of PCA up to 2 hr before fear-retention testing also produced the retention deficit; these findings suggest some "retrieval failure." The 5-HT specificity of the PCA effect on fear retention was established by the demonstration that 5-HT-depleted rats (PCA, 2 X 10 mg/kg), but not NA-depleted rats, showed a nearly complete blockade of the fear-retention deficit. These experiments describe a role for 5-HT in both memory storage and retrieval processes.

Animals↗
PubMed1981

On the interactive role of central noradrenaline neurons and corticosterone in two-way active avoidance acquisition in the rat.

The noradrenaline (NA) neurotoxin, DSP4, caused a marked impairment of two-way active avoidance acquisition. Pretreatment with desipramine, which inhibits the degeneration of NA neurons by DSP4, consistently blocked the avoidance deficit. Daily treatment with corticosterone (2 X 1 mg/kg, s.c.) also blocked the impaired acquisition of avoidance induced by DSP4 but failed to affect the increase in cortical beta-noradrenergic receptors induced by DSP4. The present findings give further evidence for the important role interactions between the pituitary-adrenal axis and the locus coeruleus NA system play in aversive learning.

Animals↗
PubMed1981

The acute effect of p-chloroamphetamine on the retention of fear conditioning in the rat: evidence for a role of serotonin in memory consolidation.

The acute effect of the 5-hydroxytryptamine (5-HT) releasing compound p-chloroamphetamine (PCA) on the acquisition and retention of shock-elicited fear conditioning to the contextual cues of a normal two-compartment shuttlebox in the rat was studied in three experiments. PCA (5 mg/kg) did not impair the acquisition of fear conditioning (Experiment 1). PCA, administered either 30 or 60 min before fear conditioning, caused a total blockade of fear retention when tested 24 h after acquisition. This retrograde amnesic effect was blocked by the 5-HT uptake blocker zimelidine (10 mg/kg) when PCA was injected 60 min before shock. These findings indicate that 5-HT neurones, possibly in the forebrain, may exert an inhibitory influence upon the long-term aspects of information consolidation in memory.

Amphetamines↗
PubMed1980

Evidence for a role of the locus coeruleus noradrenaline system in learning.

The effect of the new noradrenaline (NA) neurotoxin, DSP4, on the acquisition of one-way and two-way active avoidance responses was studied in rats. This treatment caused a marked degeneration of the locus coeruleus NA system and markedly impaired both one- and two-way avoidance acquisition. Both effects were blocked by pretreatment with desipramine, a NA uptake blocking agent. The present findings support the hypothesis that the locus coeruleus NA system in its entire extent may play a role in aversive learning.

Amines↗