Biomedical subjects

T Humby

Publications and source records attributed to T Humby.

23 records · Page 2Linked to original sources

PubMed1994

Social isolation in the rat produces developmentally specific deficits in prepulse inhibition of the acoustic startle response without disrupting latent inhibition.

A series of experiments examined the effects of 8 weeks of social isolation on spontaneous locomotor activity, prepulse inhibition (PPI) of the acoustic startle response, latent inhibition (LI) in a conditioned suppression paradigm, and basal and d-amphetamine stimulated dopamine (DA) release in the ventral striatum, as measured by in vivo microdialysis. Both isolation-reared animals (those isolated from the weaning age) and isolation-housed animals (those isolated as adults) were hyperactive when placed in a novel environment. Social isolation also led to deficits in PPI of the acoustic startle response that were specific to isolation-reared animals. Isolation rearing was without effect on the expression of LI but did lead to an enhanced response to systemic d-amphetamine in terms of striatal DA release. The data are discussed with respect to the involvement of ventral striatal DA mechanisms in the expression of PPI and LI, differences in the impact of social isolation in young and adult animals, and the utility of social isolation model as a nonlesion, nonpharmacologic means of perturbing ventral striatal DA function.

Acoustic Stimulation↗

PubMed1993

Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia.

Schizophrenic patients exhibit deficits in the prepulse inhibition of startle, an operational measure of the sensorimotor gating deficits that are theorized to contribute to cognitive disorganization. In rats, the activation of mesolimbic dopamine (DA) disrupts prepulse inhibition, providing a useful model of the similar deficits in sensorimotor gating in schizophrenic patients. Rats reared in isolation exhibit neurochemical and behavioral abnormalities suggestive of hyperactivity in mesolimbic DA systems. In the present studies, rats reared in social groups or in isolation were tested in startle response paradigms using 120 or 105 dB acoustic pulses, some of which were preceded (100 msec) by prepulses that were 2, 4, 8, or 16 dB above the 65 dB background. Isolation-reared animals were hyperreactive only in response to the initial few startle stimuli. The amount of prepulse inhibition was decreased significantly in isolation-reared animals, particularly when midrange 8 dB prepulses were used. A subsequent study replicated the effect of isolation rearing on prepulse inhibition and suggested that the deficit in sensorimotor gating exhibited by isolation-reared animals may be normalized by the administration of the DA antagonist raclopride (0.05 mg/kg). Hence, isolation rearing provides a nonpharmacological way to induce in rats a deficit in sensorimotor gating that is exhibited by schizophrenic patients.

Acoustic Stimulation↗

PubMed1993

Enhancement of amphetamine-induced locomotor activity and dopamine release in nucleus accumbens following excitotoxic lesions of the hippocampus.

This study tested the hypothesis that the hippocampus modulates dopamine-dependent function of the nucleus accumbens using behavioural and neurochemical evidence. Rats with bilateral lesions of the hippocampus induced by colchicine and kainic acid exhibited equivalent levels of spontaneous locomotor activity but a potentiation of the hyperactivity produced, dose-dependently, by D-amphetamine measured in photo-cell activity cages. The same rats subsequently received unilateral implantations of a microdialysis probe aimed at the nucleus accumbens and showed elevated levels of extracellular dopamine in response to D-amphetamine but no significant difference in basal values in comparison with sham-operated controls. The results are discussed in terms of functional interactions between the hippocampus and nucleus accumbens involving the control of mesolimbic dopamine release.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1992

Circadian and photoperiodic time measurement in male Syrian hamsters following lesions of the melatonin-binding sites of the paraventricular thalamus.

Autoradiographic studies using [125I]iodomelatonin in several species, including the Syrian hamster, have revealed that the rostral region of the anterior paraventricular nucleus of the thalamus (aPVT) contains a very high density of binding sites for melatonin. In two studies, small or large bilateral electrolytic lesions of the aPVT were made in adult male hamsters maintained on long days (LD 16:8). The hamsters were then transferred to short days (LD 8:16) to test whether testicular regression could occur in response to a decrease in photoperiod. Serum prolactin concentrations were measured as a second photoperiodic response. All unoperated control hamsters showed the typical short-day photoperiodic response: A decrease in serum luteinizing hormone (LH) and prolactin concentrations and testicular regression all occurred within 6 weeks in short days, followed by the development of scotorefractoriness. Lesions of the aPVT did not significantly affect the rate or the degree of the short-day-induced decline in serum levels of LH or prolactin, nor the pattern of testicular regression and the subsequent expression of refractoriness. To enable us to determine whether the aPVT might be involved in the entrainment or the expression of circadian rhythms, locomotor activity was monitored continuously in lesioned and control groups in Experiment 2, prior to and following the switch to short days. The reduction in photoperiod (involving an 8-hr advance in the time of lights-off and an 8-hr extension of the dark phase) caused a decompression of the nocturnal activity bout of control animals, so that after 2 weeks in short days, activity onset had also advanced to regain its phase relationship to the timing of lights-off. A similar pattern of reentrainment was observed in lesioned animals, and no differences were observed between treatment groups in the rate of entrainment and decompression. In addition, both intact controls and animals bearing large bilateral lesions of the aPVT exhibited robust free-running circadian rhythms of locomotor activity when held under constant dim red light. In summary, the integrity of the aPVT is not necessary for the seasonal response of the reproductive axis and prolactin secretion to photoperiod, nor for photic entrainment of activity rhythms, in the Syrian hamster.

Animals↗

PubMed1992

A nonphotic stimulus causes instantaneous phase advances of the light-entrainable circadian oscillator of the Syrian hamster but does not induce the expression of c-fos in the suprachiasmatic nuclei.

The study investigated whether nonphotic cues that alter the phase of overt circadian rhythms do so by causing instantaneous shifts in the underlying, light-sensitive clock. Wheel-running activity in Syrian hamsters was studied under free-running conditions of constant dim red light as an overt marker of circadian phase, the daily onset of activity being defined as circadian time 12 (CT 12). Exposure to a 15 min pulse of bright light at CT 12.20 caused a phase delay in activity onset, whereas pulses delivered at CT 11.20 had no effect upon the overt rhythm. Correlated with their effect on behavior, light pulses delivered at CT 12.20 induced expression of c-fos-like immunoreactivity in the retinorecipient regions of the suprachiasmatic nuclei of the hypothalamus (SCN), whereas pulses delivered at CT 11.20 had no effect upon the expression of c-fos. Expression of this immediate-early gene therefore provided a second marker of circadian phase, because its induction by light is closely correlated with the onset of subjective night (CT 12). To establish a suitable protocol for nonphotic shifts of the activity rhythm, animals were handled and received a subcutaneous injection of saline at different circadian phases. Injections at CT 8 or CT10 caused an immediate bout of wheel-running activity, and a consequent phase advance in the activity rhythm as assessed by the earlier onsets of activity in successive days. Handling and injections at other circadian phases were without effect. Despite shifting the overt rhythm, these procedures at CT 10 did not lead to the expression of c-fos in the SCN.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗