Repetitive Head Movements Research Articles

Muscimol microinfused into the nigrotegmental target area blocks selected components of behavior elicited by amphetamine or cocaine.

We examined whether behaviors elicited by systemic administration of the stimulants amphetamine and cocaine involve the relay of outflow from basal ganglia to the target region of the GABAergic nigrotegmental pathway (nigrotegmental target area: NTT), in the region of the pedunculopontine nucleus. Bilateral microinfusions of the GABAA agonist muscimol (25 ng in each side) were administered into the NTT in stimulant-treated rats. Amphetamine- and cocaine-induced stereotyped sniffing and repetitive head movements were totally abolished by muscimol infusions. In contrast, stimulant-induced locomotion and snout contact fixation were spared or enhanced. These observations, which extend those of Childs and Gale (1983b) with apomorphine-induced gnawing, further implicate the GABAergic nigrotegmental pathway in the mediation of basal ganglia-related motor dysfunction. On the other hand, cocaine- and amphetamine-induced locomotion and snout contact fixation do not appear to depend upon mediation through GABA-receptive neurons in the NTT. Thus, the NTT may be selective for the processing of outflow from the basal ganglia.

Evidence for multiple opiate receptor involvement in different phencyclidine-induced unconditioned behaviors in rats.

Rats were used for comparing the behavioral response profiles of phencyclidine (PCP) and d,1-N-allylnormetazocine (NANM), two drugs that are proposed to exert their effects through the "PCP/sigma" receptor. Phencyclidine (1.0-5.0 mg/kg) and NANM (2.5-10.0 mg/kg) induced dose-related increases in locomotion, sniffing, repetitive head movements, non-object directed mouth movements, and ataxia. Both drugs also increased food and water consumption during the latter portion of the drug response. Ingestive behaviors induced by PCP (2.5 mg/kg), as with eating and drinking stimulated by the mu-opiate morphine (2.0 mg/kg), were blocked by a relatively low dose of the opiate antagonist naloxone (0.5 mg/kg). Multiple injections of PCP (2.5 mg/kg for 4 days) or NANM (10.0 mg/kg for 4 days) augmented several measures of behavioral activation, including horizontal locomotion, rearing, and nonfocused sniffing, but did not significantly change stereotyped behaviors or ataxia. Reciprocal cross-sensitization of locomotor activation is indicated by the finding that the response to a challenge injection of PCP (2.5 mg/kg) or to NANM (10.0 mg/kg) after 4 days of treatment with the other drug closely resembled the enhanced locomotor response observed after the chronic treatment. Phencyclidine and NANM thus appear to exert many of their effects on unconditioned behavior through common mechanisms, including interaction with sigma receptors. In addition, these findings are consistent with previous suggestions that a mu-opiate receptor system may modulate some effects of PCP.

Evidence that thioridazine enhances amphetamine-induced stereotypy via anticholinergic activity

1. 1. The hypothesis that the anticholinergic properties of thioridazine can account for its ability to enhance amphetamine-induced stereotyped behaviors was tested. 2. 2. In one experiment, scopolamine-induced repetitive head movements were shown to be potentiated by thioridazine. 3. 3. In another experiment, subthreshold doses of scopolamine and thioridazine interacted to potentiate amphetamine-induced repetitive head movements. 4. 4. The data suggest that thioridazine, in addition to its neuroleptic activity, has significant anticholinergic effects in vivo and these effects may account for its potentiation of amphetamine-induced stereotypy.

Acute and chronic behavioral interactions between phencyclidine (PCP) and amphetamine: Evidence for a dopaminergic role in some PCP-induced behaviors

Amphetamine and phencyclidine (PCP) are both proposed to exert effects on unconditioned behavior through dopaminergic mechanisms. However, a relatively complete characterization of their effects in rats reveals markedly different response profiles. Furthermore, whereas acute co-administration of amphetamine and PCP resulted in an increase in one component of stereotypy, repetitive head movements, two measures of locomotor activation, i.e., ambulation and nonfocused sniffing, were unchanged, and rearings were reduced. In addition, the response alterations which occur with repeated administration of these drugs did not display cross-sensitization. Thus, although repeated daily injections of amphetamine, which produced progressive locomotor augmentation, sensitized animals to the locomotor-stimulating effects of PCP, repeated PCP treatment, which also resulted in locomotor augmentation, decreased the locomotor response to a challenge injection of amphetamine. These findings suggest significant differences in the mechanisms underlying the effects of acute and repeated administration of PCP and amphetamine.

Opposite effects of sulpiride and metoclopramide on amphetamine-induced stereotypy

The effects of the atypical neuroleptic sulpiride (0–20 mg/kg s.c.) and the classical neuroleptic metoclopramide (0–4 mg/kg s.c.) on behaviours produced by D-amphetamine (0–5 mg/kg i.p.) were measured in a time-sampling observational paradigm in rats. Sulpiride had one clear dose-dependent effect: it enhanced amphetamine-induced stereotyped behaviours (repetitive head movements, sniffing down and some gnawing). In contrast, metoclopramide dose-dependently decreased amphetamine-induced stereotypy, locomotion, rearing, and sniffing up, and concurrently antagonized the suppression of lying down produced by amphetamine. Sulpiride's facilitatory effects on amphetamine-induced stereotypy follow a pattern previously observed for two other atypical neuroleptics: clozapine and thioridazine. This may be a common effect of atypical neuroleptics. Since these neuroleptics are antipsychotic, amphetamine-induced stereotypy appears to be a poor animal model for human psychoses. It is suggested that sulpiride's effects may be mediated through a preferential presynaptic versus postsynaptic action on dopamine neurons in the nigrostriatal bundle.

Repetitive head movements during REM sleep

Repetitive head movements during REM sleep

Apparent tolerance to some aspects of amphetamine stereotypy with long-term treatment

Previous reports have demonstrated that long-term amphetamine treatment results in a progressive augmentation of locomotion and focused stereotypy in the rat. A series of experiments were conducted to determine whether an increase in dopamine receptor sensitivity is the primary mechanism underlying the behavioral alterations associated with multiple amphetamine injections. Detailed observations of the focused stereotyped behaviors produced by amphetamine revealed that although some components were enhanced with long-term treatment, others were reduced. Thus, whereas repeated administration of 2.5 mg/kg d-amphetamine produced a progressive increase in repetitive head and limb movements, long-term treatment with 5.5 mg/kg d-amphetamine resulted in a reduction of licking and biting behaviors (oral stereotypies). These results, which suggest that different mechanisms mediate the various components of focused stereotypy, argue against the supersensitivity hypothesis. In fact, the apparent tolerance that develops to oral stereotypies may reflect a decrease in dopamine receptor sensitivity since repeated amphetamine administration also reduces the oral stereotypies produced by 0.5 or 2.0 mg/kg apomorphine, a direct acting dopamine agonist. Thus, the behavioral alterations produced by repeated amphetamine injections cannot be explained solely by an increase in receptor sensitivity.

Evidence that the different properties of haloperidol and clozapine are not explained by differences in anticholinergic potency.

In previous studies we have shown that neuroleptic drugs are distinctly different in their ability to antagonize apomorphine-induced behavioural activation. Comparison with clinical data indicated that antipsychotic drugs causing extrapyramidal side effects (EPS), like haloperidol, efficiently antagonized apomorphine-induced gnawing and in higher doses also apomorphine-induced locomotion, while drugs with a low incidence of EPS, like clozapine, antagonized only locomotion, sniffing, and repetitive head and limb movements, and could even potentiate the gnawing. The difference between haloperidol and clozapine in the incidence of EPS has been tentatively explained by the fact that clozapine has an anticholinergic action apart from its ability to block dopamine receptors. As an indirect test of this hypothesis we have made use of the difference in the ability to antagonize apomorphine-induced behaviour and tested whether a combination of haloperidol and an anticholinergic drug (scopolamine) can mimick the characteristic effect of clozapine on apomorphine-induced behaviour. We found that the pattern of behaviour elicited by apomorphine after combined haloperidol and scopolamine pretreatment was characterized by sniffing and repetitive head and limb movements. This patter of behaviour showed a clear dose-response characteristic in that the intensity of the stereotypies was increased with increasing doses of scopolamine. However, it was not possible to induce strong compulsive gnawing, which is pattern of behaviour elicited by apomorphine after high doses of clopazine. These results therefore support the idea that the different properties of haloperidol and clozapine cannot be explained by differences in anticholinergic potencies.

A study of the changes in motor behaviour caused by TRH on intracerebral injection

20 μg TRH injected bilaterally into the caudate-putamen, tuberculum olfactorium, nucleus accumbens, amygdala, lateral ventricles, midbrain or cerebral cortex failed to induce any increase in locomotor activity (measured using photocells), although other behavioural changes were observed after each injection, and induced body shakes, limb tremor, repetitive head and limb movements, biting, scratching and an alert appearance. These behavioural changes could result in positive readings from equipment used to measure locomotor activity, but careful investigations focussing on the nucleus accumbens used photocell boxes, activity wheels and Animex recorders to emphasise the inability of intracerebral TRH (10–40 μg) to enhance locomotor activity. Intraaccumbens TRH also failed to enhance amphetamine hyperactivity or reduce the motor depression caused by haloperidol and analeptic drugs. The data do not support a central locomotro stimulant action for TRH.

Toxic effects of postnatal administration of streptomycin sulfate to rats

Postnatal rats were given 300 mg/kg sc of streptomycin sulfate daily from 2 to 22 days of age and observed for toxic effects over an 8-month period. Abnormal motor activity, including backward locomotion, circling, and repetitive head movements, persisted for several weeks or months after dosing was stopped. Hyperactivity, deafness, and impaired righting reflex persisted throughout the experimental period. Decreased body weight, delayed incisor eruption, decreased tibia length in females, delayed vaginal opening, increased exploratory activity of females, and decreased fertility of females were also observed. Time of ear and eye opening, tail length, estrous cycle regularity, temperature regulation, and adrenal and liver weights appeared normal. Ophthalmoscopic, hematologic, and histologic examinations revealed no abnormalities.

Apomorphine-induced locomotion and gnawing: Evidence that the experimental design greatly influences gnawing while locomotion remains unchanged

In a recent study we have shown that it was possible to recognize and record two independent behavioural patterns elicited by apomorphine (s.c.): one behaviour characterized by increased locomotion, sniffing and repetitive head and limb movements and another, characterized by compulsive gnawing. In the present study we have further characterized the gnawing and the locomotion patterns, their dependence on the experimental design and on the test environment. We found that the apomorphine-induced gnawing was easily modified by factors such as the design of the test-box and the habituation of the animal to the test-box. Locomotion, on the other hand was essentially independent of such factors and seemed more compulsive than the so-called “compulsive gnawing”.

Different behavioural patterns induced by apomorphine: Evidence that the method of administration determines the behavioural response to the drug

The behavioural effects of s.c. injected apomorphine was studied on habituated rats in a test-box designed to measure 8 different components of behaviour. Apomorphine, 1 mg/kg, induced two different behaviours: The “G-type” of behaviour characterized by compulsive gnawing and the “LS-type” of behaviour characterized by increased locomotion, sniffing and repetitive head and limb movements. G-type behaviour was induced when apomorphine, dissolved by heating, was injected s.c. into the flank of the animal. LS-type behavior was induced both when apomorphine, dissolved by heating, was injected s.c. into the neck and when it was dissolved by heating together with a high concentration of ascorbic acid (1 mg/ml) and ijected s.c, into the flank. G-type behaviour could not be elicited by changing the dose which induced LS-type behaviour or vice versa. We therefore conclude that these different behavioural effects of apomorphine were not dose—response effects but were elicited by at least two different synaptic mechanisms in the brain. Experimentally induced changes from one of these apomorphine-induced behaviours to another can therefore not merely be interpreted as a change in the intensity of the behavioural response as is done in e.g. commonly used stereotypy rating scales.

Differences in the nature of the stereotyped behaviour induced by aporphine derivatives in the rat and in their actions in extrapyramidal and mesolimbic brain areas

Apomorphine, (-)-N-n-propylnorapomorphine [(-)-NPA] and (±)-N-n-propylnorapomorphine [(±)-NPA] each caused stereotyped behaviour patterns in the rat which could be differentiated into two components, sniffing and repetitive head and limb movements (low intensity component) and gnawing, biting and licking (high intensity component). Low intensity components occurred at low doses of apomorphine and high intensity components at larger doses but the two components never occurred independently for (-)-NPA or (±)-NPA. Biting was the predominant effect of these agents which were shown to be at least twenty times more potent than apomorphine. The (-)-isomer of NPA was the more potent. The two components of stereotypy were differentiated both pharmacologically (using amantadine, reserpine plus α-methyl-p-tyrosine and haloperidol) and by lesions placed in areas of the extrapyramidal (caudate-putamen, globus pallidus, substantia nigra) and mesolimbic (nucleus accumbens septi, tuberculum olfactorium, nucleus amygdaloideus centralis) systems. However, both sniffing and biting responses were reduced by lesions of the serotonergic raphe nuclei. The two stereotypic components were differentially induced by intracerebral injections of apomorphine and (-)-NPA into the caudate-putamen, nucleus accumbens septi and tuberculum olfactorium. Injections into the central nucleus of the amygdala were ineffective. The degree of involvement of the different areas was shown to differ for apomorphine and (-)-NPA, in particular the nucleus accumbens septi appeared more important for the action of (-)-NPA and the tuberculum olfactorium for apomorphine. Intracaudate (-)-NPA was less active than apomorphine but, generally, intracerebrally applied (-)-NPA was twice as potent as apomorphine. Both (-)-NPA and apomorphine caused circling behaviour in animals with asymmetric medial raphe nucleus lesions (contralateral) or unilateral lesions of the substantia nigra (ipsilateral). In these experiments (-)-NPA was ten times more potent than apomorphine.

Extrapyramidal and mesolimbic involvement with the stereotypic activity of D- and L-amphetamine

The electrolytic brain lesion technique was use to investigate the role of the dopamine-containing areas and pathways of the extrapyramidial and mesolimbic systems in the mediation of the stereotyped behaviour patterns induced by D- and L-amphetamine in the rat. Interruption of the ascending dopaminergic neurones from the mesencephalon at the level of the lateral hypothalamus did not modify the dose-dependent stereotypy induced by D- or L-amphetamine, whilst a lesion placed in the rostral hypothalamus to interrupt the dopaminergic innervation to the mesolimbic brain areas was shown to abolish the wearker intensity component of stereotypy (sniffing and repetitive head movements). Of the areas innervated by this pathway, lesion of the tuberculum olfactorium, but not the nucleus interstitialis stria terminalis or nucleus accumbens septi, also abolished sniffing behaviour. Lesions placed in the neostriatal area of the extrapyramidal system were without significant effect whilst lesion of the paleostriatum abolished all components of stereotypy. Lesion of the central amygdaloid nucleus only abolised the more intense components of both D- and L-amphetamine stereotypy (bitting, gnawing and licking). The brain studies demonstrate a differential involvement of the dopamine-containing areas of the mesolimbic and extrapyramidal brain regions, and the associated dopaminergic neurones which ascend from the mesencephalon, with the stereotyped behaviour patterns induced by both D- and L-amphetamine.