Tail-pinch stimulation: sufficient motivation for learning.

A paper clip applied to the tails of rats induced gnawing and eating, which decreased in latency and increased in duration with experience. With sustained pressure to the tail, rats learned a new habit in order to gain access to wood chips on which to gnaw. That these are also properties of behavior elicited by electrical brain stimulation suggests that both manipulations may act through the same mechanism. These results support the hypothesis that a nonspecific arousing stimulus can be a sufficient condition for establishing learned habits.

Nigral transplants reinnervating the dopamine-depleted neostriatum can sustain intracranial self-stimulation.

Transplants of embryonic substantia nigra reinnervated the striatum and were able to sustain intracranial self-stimulation in rats with brain lesions induced by 6-hydroxydopamine. Dopaminergic drugs and alterations in current intensity produced typical changes in response rates. Animals with electrodes implanted into cortical grafts or into the denervated striatum failed to exhibit self-stimulation. These findings suggest that transplanted dopamine neurons convey specific, temporally organized information axonally to the striatum.

The effects of lesions to ascending noradrenergic neurons on discrimination learning and performance in the rat.

Three experiments examined the effect of central noradrenergic depletion on the acquisition and performance of a temporal discrimination in auditory or visual modalities. In Experiment 1, 6-hydroxydopamine-induced lesions of the dorsal noradrenergic bundle significantly retarded acquisition compared to a similarly lesioned ventral noradrenergic bundle-group, two sham-operated and one unoperated control group. In Experiment 2, the acquisition impairment produced in the dorsal noradrenergic bundle group was replicated, for both auditory and visual modalities, by lesions depleting hippocampal and neocortical noradrenaline by over 80%. In rats subsequently switched to discriminations involving the unfamiliar modality, the dorsal-bundle lesion also impaired acquisition several weeks after surgery. Experiment 3 showed significantly impaired performance in rats with dorsal bundle lesions when training prior to surgery had not resulted in better than chance performance. In rats previously trained to criterion, the dorsal bundle lesion transiently, but non-significantly, impaired performance. In rats performing better than chance, but not having reached criterion, there were no significant effects of the dorsal bundle lesion. Subsequent manipulations of deprivation and difficulty of discrimination in general failed to distinguish between the dorsal bundle lesion and sham-groups, suggesting that the acquisition impairment did not result from simple sensory or motivational effects. Reducing the interstimulus interval did impair the dorsal bundle group more than controls. However, there was no evidence of altered "distractibility" in the lesioned group when the alternative modality was introduced as a distractor. The results are discussed in terms of other acquisition deficits shown by rats with central noradrenaline depletion and their significance for determining the functions of the projections from the locus caeruleus via the dorsal noradrenergic bundle to the neocortex and hippocampus.

An observational method for quantifying the behavioural effects of dopamine agonists: contrasting effects of d-amphetamine and apomorphine.

A novael means of measuring and analysing behavioural effects of dopamine agonists is described and illustrated by a comparison of the effects of d-amphetamine and apomorphine in the rat. d-Amphetamine (0--15 mg/kg IP) produced significant dose- and time-dependent changes in responses such as locomotion, rearing and sniffing, but not in licking or gnawing. In contrast, apomorphine (0--5 mg/kg SC) produced significant increases in licking and gnawing, as well as in locomotion and sniffing, but no changes in rearing. The results are discussed in comparison with those obtained by other methods, such as photocell beam interruptions or sterotypy rating scales, and may be of importance in elucidating the functions of the forebrain dopamine projections.

Asymmetry in the effects of unilateral 6-OHDA lesions on eating and drinking evoked by hypothalamic stimulation.

The present experiment investigated the effects of unilateral 6-hydroxydopamine lesions of the caudate nucleus and nucleus accumbens on eating and drinking evoked by electrical stimulation of the lateral hypothalamus (ESLH). Lesions were made on either the 'dominant' or 'non-dominant' hemisphere as defined by an amphetamine-rotation test. We report here that lesions of the 'dominant hemisphere' were significantly more effective in disrupting ESLH-evoked behavior as well as producing longer-lasting deficits in somatosensory responsiveness as measured by the 'tactile extinction test'.

Self-stimulation at the lateral hypothalamus and locus coeruleus after specific unilateral lesions of the dopamine system.

A group of rats was trained to press levers for electrical stimulation from bipolar electrodes aimed at the lateral hypothalamus (LH), and another group was trained to self-stimulate from electrodes in the locus coeruleus (LC). All rats in both groups were subjected to unilateral injections of 6-hydroxydopamine into the substantia nigra and midbrain ventral tegmentum. The lesions produced profound depletions of dopamine from the ipsilateral frontal cortex, nucleus accumbens/olfactory tubercle, and corpus striatum. Pretreatment with desmethylimipramine prevented loss of noradrenaline in excess of that caused by electrode implantation. The destruction of the dopamine projections produced a persistent and pronounced deficit in intracranial self-stimulation from ipsilateral electrodes in both the LH and LC groups, but only transient effects on self-stimulation from contralateral electrodes at these sites. These results suggest that an intact dopamine system is required for the expression of self-stimulation behaviour.

A comparison of two different methods for the measurement of drinking in the rat.

Drinkometers based on two different principles are described and compared. A capacitative design relied on the detection of a very small current through the animal as a means of recording contacts between the animal's tongue and the drinking spout. A photocell-based design relied on a beam across the front of the drinking spout being broken by the animal's tongue as a record of access to the spout. Both types of device were found to give a picture of the animal's behaviour similar to that obtained by a measure of the volume of fluid ingested. However the devices using a photocell were found to be less prone to error than the capacitative devices.

CANTAB battery: proposed utility in neurotoxicology.

The CANTAB battery was developed for the assessment of cognitive deficits in humans with neurodegenerative diseases or brain damage. It consists of a series of interrelated computerized tests of memory, attention, and executive function, administered via a touch sensitive screen. It allows a decomposition of complex tasks commonly used in clinical assessment into their cognitive components and enables the extrapolation of findings from the animal literature. Tests include versions of the Wisconsin Card-Sorting Test and the Tower and London and also the Delayed Matching-to-Sample test, widely used in monkeys for visual recognition memory. The tests are constructed in such a way that they may be given to animals (monkeys) with minimal change. The nonverbal nature of the CANTAB tests makes them largely language independent and culture free. CANTAB has been standardized on a large, predominantly elderly, population and validated in neurosurgical patients as well as in patients with basal ganglia disorders, Alzheimer's disease, depression, and schizophrenia. In addition, CANTAB has been used to evaluate: a) the therapeutic effects of dopaminergic and cholinergic medication in neurodegenerative disease; b) cognition in 5-11-year-old normal, learning-disabled, and autistic children; c) deficits in patients with HIV infection; and d) early, asymptomatic Huntington's disease. The latter illustrate its usefulness in early identification of progressive disorders. It is suggested that the battery should have particular utility across a wide range of age and intelligence in longitudinal assessment after exposure to toxicants, and allow meaningful comparison with experimental studies of toxic effects in other species.