Neurobiology of D1 Dopamine Receptors after Neonatal-6-OHDA Treatment: Relevance to Lesch-Nyhan Disease

Gr, Breese; Ra, Mueller; Tc, Napier; Ge, Duncan

doi:10.1007/978-1-4684-5191-7_13

Cited by 42 publications

(11 citation statements)

References 31 publications

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“…However, the possibility remains that alterations in serotonergic or other neurotransmitter function, and not antagonism of DA receptor function, by olanzapine underlie the observed efficacy against selfinjury in neonate-lesioned animals. Overall, the results support the use of olanzapine in clinical syndromes that may involve aberrant behaviors, such as those observed in Lesch-Nyhan disease and some types of mental retardation (Lloyd et al 1981;Breese et al 1986). …”

Section: Discussionsupporting

confidence: 65%

Effect of Olanzapine on Functional Responses from Sensitized D1-Dopamine Receptors in Rats with Neonatal Dopamine Loss

Moy

Knapp

Breese

2001

Neuropsychopharmacology

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(Breese et al. 1985a,b). For example, neonate-lesioned animals have increased locomotion following treatment with SKF-38393, a D 1 -DA receptor agonist, at doses that have minimal impact on control rats (Breese et al. 1985a,b). Repeated treatment with D 1 -DA agonists can lead to extremely high rates of activity in lesioned rats, and this "priming" effect can still be observed 6 months after the chronic drug treatment (Breese et al. 1985b;Criswell et al. 1989b). Supersensitivity of D 1 -DA receptors in neonatal-6-OHDA rats has also been linked to stereotyped responses and self-injurious behavior (SIB) following treatment with L-Dopa or apomorphine, suggesting that these animals can provide a valuable model for the self-injury and DA loss associated with Lesch-Nyhan disease (Breese et al. 1984a,b), a metabolic disorder primarily observed in male children (Lesch and Nyhan 1964).Paradoxically, although the aberrant responses in the neonate-lesioned rats can be completely blocked with selective D 1 -DA receptor antagonists (Breese et al. 1985a), these animals are remarkably subsensitive to haloperidol, even at doses which induce catalepsy in normal controls and in rats given 6-OHDA as young adults (Bruno et al. 1985;Duncan et al. 1987). Similarly, treatment with typical antipsychotic agents does not prevent the painful self-injury that occurs in LeschFrom the Departments of Psychiatry (SSM, DJK, GRB), Anesthesiology (GRB) and Pharmacology (GRB), Skipper Bowles Center For

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Section: Discussionsupporting

confidence: 65%

Effect of Olanzapine on Functional Responses from Sensitized D1-Dopamine Receptors in Rats with Neonatal Dopamine Loss

Moy

Knapp

Breese

2001

Neuropsychopharmacology

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“…Morelli et al (Morelli and Di Chiara, 1990;Morelli et al, 1992) demonstrated that MK-801 potentiated DA D 1 -mediated responses but reduced DA D 2 -mediated responses in the unilateral 6-OHDA model of Parkinsonism; it has been suggested that the neonatal 6-OHDA lesions and the unilateral 6-OHDA lesions may induce comparable adaptations in dopaminergic systems (Moy et al, 1997). It has been reported that the locomotor stimulant effect of apomorphine is primarily associated with the DA D 2 receptor site Breese et al, 1986;Schechter and Greer, 1987), which seems to fit the present observation of MK-801-reduction of apomorphine supersensitivity. It ought to be noted that this MK-801-reduction of apomorphine supersensitivity was expressed largely by locomotor behaviour and total activity but not rearing behaviour.…”

Section: Discussionmentioning

confidence: 94%

Behavioural supersensitivity following neonatal 6-hydroxydopamine: Attenuation by MK-801

Archer

Fredriksson

2007

neurotox res

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Male rat pups were administered 6-hydroxydopamine (6-OHDA, 75 microg, intracisternally, 30 min after desipramine, 25 mg/kg, s.c.) on Days 1 or 2 after birth, or were sham-operated (receiving vehicle). In four experiments, the acute effects of apomorphine, with or without pretreatment with MK-801 (0.03 mg/kg), upon motor activity in test chambers was measured. Acute treatment with apomorphine (0.1 mg/kg) increased locomotor, rearing and total activity markedly compared to both the acute saline administered 6-OHDA rats and the sham-operated rats administered saline. Acute MK-801 (0.03 mg/kg) co-administered shortly before (5 min) apomorphine (0.3 or 1.0 mg/kg) reduced markedly locomotion and total activity in 6-OHDA-treated and sham-operated rats. Rearing behaviour was increased in both the 6-OHDA groups of rats. Acute MK-801 increased activity in the 6-OHDA-treated rats, which was not observed in sham-operated rats. At the 0.3 and 1.0 mg/kg doses of apomorphine, neonatal 6-OHDA treatment increased all three parameters of motor activity. Acute treatment with apomorphine (0.1 mg/kg) induced different effects on the motor activity of 6-OHDA-treated and sham-operated mice. In sham-operated rats apomorphine reduced motor activity during the 1st 30-min period but increased locomotion and total activity, but not rearing, during the 2nd and 3rd periods, whereas in 6-OHDA-treated rats, apomorphine increased locomotor, rearing and total activity markedly. Dopamine loss and serotonin elevation in the striatum and olfactory tubercle were confirmed. The present findings confirm the influence of non-competitive glutamate antagonists in attenuating the behavioural supersensitivity to dopamine antagonists.

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“…Automutilation, as an extreme stereotypic behaviour, has been shown in animal experiments to be triggered by an imbalance of certain neuropeptides (Cools &. van den Bercken 1977, Breese et al 1986, Cabib et al 1984, Moon et al 1980. As well, certain stereotypic Iglauer et al behavioural patterns have been described to occur with increased levels of dopamine or morphine agonists (dosage dependent) in spontaneous cases seen in man or other mammals (Coid et al 1983, Dodman et al 1988a, Dodman et al 1988b.…”

Section: Discussionmentioning

confidence: 99%

Hereditary compulsive self-mutilating behaviour in laboratory rabbits

et al. 1995

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During the last few years an increasing number of cases of extensive automutilation has been observed in a rabbit breeding colony of Checkered crosses. Digits and pads of the front feet were traumatized. No other behavioural abnormalities or signs of disease were evident. Self-mutillation was seen both in stock, breeding and experimental animals, in rabbits kept singly in cages and in those housed in groups on the ground, in rabbits kept in different buildings and under the care of different staff members. This behavioural abnormality of Checkered crosses has also been observed in animals after being placed into other institutions or private homes. No evidence of an agent responsible for the occurrence of self-injury could be found with parasitological, mycological, histological, clinical or haematological examination. Twelve to 16 animals are affected yearly in a colony varying in size between 130 and 230 rabbits. Following complete healing, relapses occurred up to 3 times per year, on either the same or the opposite front foot. In the last 21 cases episodes of automutillation could be regularly interrupted with the dopamine antagonist, haloperidol. Similar signs of auto-mutillation were never seen in animals of another breeding line kept in the same building and under the same conditions nor in animals brought in from other breeding colonies. A relatively high coefficient of inbreeding can be presupposed in this 15-year-old breeding colony of Checkered crosses. A genetic predisposition for the behavioural anomaly described appears very likely.

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Neurobiology of D1 Dopamine Receptors after Neonatal-6-OHDA Treatment: Relevance to Lesch-Nyhan Disease

Cited by 42 publications

References 31 publications

Effect of Olanzapine on Functional Responses from Sensitized D1-Dopamine Receptors in Rats with Neonatal Dopamine Loss

Effect of Olanzapine on Functional Responses from Sensitized D1-Dopamine Receptors in Rats with Neonatal Dopamine Loss

Behavioural supersensitivity following neonatal 6-hydroxydopamine: Attenuation by MK-801

Hereditary compulsive self-mutilating behaviour in laboratory rabbits

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