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Biomedical subjects

A K Mohammed

Publications and source records attributed to A K Mohammed.

33 records · Page 2Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Persistent changes in behaviour and brain serotonin during ageing in rats subjected to infant nasal virus infection.

Suckling rats were infected intranasally with the temperature-sensitive mutant G41 strain of vesicular stomatitis virus. The rats survived but demonstrated lifelong learning deficits in the Morris maze and impaired exploratory behaviour in the open field test. When examined at 18 months of age they had a severe loss of neurons in the medial and dorsal raphe nuclei in the brain stem and reduced levels of serotonin and its metabolite 5-hydroxyindole acetic acid in the cerebral neocortex and hippocampus. The levels of noradrenaline, dopamine, homovanillic acid, 3,4-dihydroxyphenylacetic acid, choline acetyltransferase and glutamate decarboxylase were largely unaffected. The permanent disturbance in brain serotonin metabolism did not cause any histological changes in the cerebral cortex. Thus there were no neurofibrillary tangles or amyloid plaques as has been reported as a late effect of chemically induced lesion to the cholinergic system in the rat brain. It is concluded that the brain serotonergic system is especially vulnerable to an episode of virus attack along olfactory pathways and that the neurochemical and behavioural alterations caused by such an episode persist during a major part of the animal's life span.

Aging↗

Immunohistochemical and behaviour pharmacological analysis of rats inoculated intranasally with vesicular stomatitis virus.

A temperature-sensitive mutant of vesicular stomatitis virus was inoculated intranasally into infant Sprague-Dawley rats aged 9 to 17 days. Rats receiving the virus at 9 days of age had an extensive spread of infection throughout the brain and the animals died after a few days. Rats inoculated at day 11 postnatally survived and the infection was limited to the olfactory pathways, hypothalamus, diagonal bands and the anterior raphe nuclei. Stereological measurements showed that the volume of infected neurons constituted 67 +/- 10% of the total neuronal volume in the dorsal raphe nucleus. Double-labelling experiments revealed that both 5-hydroxytryptamine- and substance P-immunoreactive neurons contained the virus antigen. The motor stimulant effect of amphetamine was studied at 3 months post infection. The increase in amphetamine-induced frequency and duration of rearing was significantly attenuated in infected rats and the amphetamine-induced locomotion was slightly reduced.

Administration, Intranasal↗