Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei

Costall, B.; Marsden, C. D.; Naylor, R.J.; Pycock, Christopher J.

doi:10.1016/0006-8993(77)90645-x

Cited by 217 publications

(57 citation statements)

References 47 publications

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“…Locomotion induced by low doses of AMPH is thought to be mediated mainly by DA activity in the meso-accumbens DA pathway, based on studies employing lesions of DA pathways, pharmacological manipulation of DA and noradrenaline transmission, and metabolic mapping with 2-deoxyglucose (e.g., Creese and Iversen 1975;Roberts et al 1975;Costall et al 1977;Porrino et al 1984). …”

Section: Discussionmentioning

confidence: 99%

“…To test if these birth procedures affected DA function of relevance to schizophrenia, several behaviors were examined in these animals as adults. AMPHinduced locomotion was measured since behavioral and biochemical studies indicate that locomotion induced by low dose AMPH is most likely due to increased activity in the meso-accumbens DA pathway (e.g., Creese and Iversen 1975;Roberts et al 1975;Costall et al 1977;Porrino et al 1984).…”

Section: Schizophrenia Is Associated With Increased Birth Complicatiomentioning

confidence: 99%

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Birth Insult Alters Dopamine-Mediated Behavior in a Precocial Species, the Guinea Pig Implications for Schizophrenia

Vaillancourt

Boksa

2000

Neuropsychopharmacology

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Schizophrenia is associated with increased birth complications, suggesting that birth complications might alter CNS dopaminergic activity later in life. In rats, Caesarean section (C-section) birth can produce long term changes in dopaminergic biochemistry and behavior. However rat brain is somewhat immature compared to human brain at birth. The current study tested if mild birth complications also alter dopamine-mediated function in a species with a more mature CNS at birth, the guinea pig. As adults, guinea pigs born by C-section showed increased amphetamine-induced locomotion and disruption of prepulse inhibition (PPI) of acoustic startle, compared to vaginally born controls. Guinea pigs born by C-section withThere is considerable evidence that enhanced mesolimbic dopaminergic activity plays an important role in some of the symptomatology of schizophrenia (e.g., Laruelle et al. 1996Laruelle et al. , 1999Breier et al. 1997; AbiDargham et al. 1998; see reviews by Seeman 1992; Lieberman et al. 1997). In addition, a large number of epidemiological studies have demonstrated that perinatal complications, often involving fetal or neonatal hypoxia, are associated with increased risk for the development of schizophrenia (e.g., Geddes and Lawrie 1995;Jones et al. 1998;Dalman et al. 1999;Hultman et al. 1999;Zornberg et al. 2000; see review by McNeil 1995).Animal modelling provides the opportunity to directly test if a birth complication, such as hypoxia, can cause long term changes in dopaminergic function. Using a rat model of global hypoxia during Caesarean section (C-section) birth, several laboratories have demonstrated that dopaminergic systems are sensitive to mild birth alterations (Bjelke et al. 1991;Loidl et al. 1994;Chen et al. 1995Chen et al. , 1997 Brake et al. 1997a,b; Boksa 1997, 1998;Vaillancourt and Boksa 1998; Berger et al. 2000a). Specifically, as adults, rats born by C-section, either with or without addition of a period of global hypoxia, show increased nucleus accumbens dopamine (DA) release in response to repeated stress (Brake et al. 1997b) Vaillancourt et al. 1999), similar to the reported increased incidence of mild respiratory distress in humans born by C-section (Hales et al. 1993).In relation to the possible clinical relevance of these results, rat brain is generally believed to be somewhat less mature at birth than is the brain of the human newborn. It has been suggested that, at approximately postnatal day 10, the brain of the rat is at the stage of rapid growth, accelerated synaptogenesis, myelinization, and astrocyte proliferation characteristic of the human newborn at term (see review by Romijn et al. 1991). Thus, the model of birth insult in the rat may relate more to premature than to term human brain. To circumvent this limitation, we initiated the current studies to test if mild birth complications also alter DA mediated function in a species with a more mature CNS at birth. The guinea pig is a precocial species, that is, capable of a high degree of independent activity at birth....

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Section: Discussionmentioning

confidence: 99%

Section: Schizophrenia Is Associated With Increased Birth Complicatiomentioning

confidence: 99%

Birth Insult Alters Dopamine-Mediated Behavior in a Precocial Species, the Guinea Pig Implications for Schizophrenia

Vaillancourt

Boksa

2000

Neuropsychopharmacology

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“…In that report, however, there was no description as to whether TRH acted on presynaptic or post synaptic sites of the DA neurons. The focal, intracerebral injection of 6-OHDA would appear to produce a selective lesion in the DA system, and this technique has been employed by some investigators to analyze the role of various DA-containing areas in behavioral effects of central stimulants, for instance, the spontaneous motor stimulatory action of DA receptor agonist is found to be markedly enhanced in rats with 6-OHDA injected either into the mesolimbic DA pathway or into the NAS containing DA nerve terminals (9,22,23). This phenomenon is thought to be due to supersensitivity by 6-OHDA.…”

Section: Effect Of Pretreatment With Pargyline or A-methyltyrosine (Amentioning

confidence: 99%

“…However, in their subsequent report (22), amphetamine-induced locomotor stimulation was not reduced in 6-OHDA lesioned rats but was significantly attenuated in pargyline and/or desipramine-pretreated 6-OHDA lesioned rats. Costall et al (23) have reported that bilateral injection of 6-OHDA into the NAS or into the DA pathway fails to modify the intensity of amphetamine hyperactivity although the duration of the effect was reduced. In the present investigation, the hyperactivity response to TRH or methampheta mine, which is probably similar to amphetamine in mode of action, was not attenuated by 6-OHDA injection into the mesolimbic DA pathway.…”

Section: Effect Of Pretreatment With Pargyline or A-methyltyrosine (Amentioning

confidence: 99%

Thyrotropin-releasing rormone: hyperactivity and mesolimbic dopamine system in rats

Miyamoto

Narumi

Nagai

et al. 1979

Japanese Journal of Pharmacology

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Abstract-The mechanism of stimulatory action of thyrotropin-releasing hormone (TRH) on spontaneous motor activity was investigated in rats. TRH produced a significant hyperactivity with intraperitoneal administration of 20 mg/kg or bilateral injection of 10 pg into the nucleus accumbens septi (NAS). Following bilateral injection of 6-hydroxydopamine into the mesolimbic dopamine (DA) pathway, the hyperactivity induced by TRH was not altered, whereas the response to apomorphine given intraperitoneally or DA injected into the NAS was clearly enhanced. The TRH-induced hyperactivity was remarkably suppressed by a-methyltyrosine and in contrast, augmented by pargyline. Systemic injection of aminooxyacetic acid in a dose producing behavioral depression reduced markedly the TRH-induced hyperactivity. Bilateral injection of ethanolamine 0-sulphate (100 pg) into the NAS produced no behavioral depression per se, but remarkably attenuated the hyperactivity response to TRH or DA (20 pg) given intraperitoneally or into the NAS. Both TRH (10-1 and 10-' M) and methamphetamine (10-6-10-4 M) increased the spontaneous release of 14C-DA from rat NAS slices . These findings suggest that TRH induces hyperactivity by enhancing DA release from nerve terminals in the NAS without a direct stimulation of the post-synaptic DA receptors. TRH and GABA, independently or via interaction between them, may play a reciprocal regulatory role in the activity of the mesolimbic DA system. Thyrotropin-releasing hormone (TRH) has central effects which may be independent of its releasing action of thyrotropin and prolactin from the anterior pituitary. These findings have been reported by different workers who found that the peptide itself produced behavioral excitation and modified behavioral effects of central depressants in intact, hypo physectomized and thyroidectomized animals (1-3). TRH is widely distributed throughout the brain and two-thirds are located outside the hypothalamus (4). Radioimmunological evidence of Hokfelt et al. (5) indicating that TRH is contained in nerve terminals of several brain regions, in particular the nucleus accumbens (NAS), is of great interest, since this nucleus is one of the most significant sites of mesolimbic dopamine (DA) system (6) and is postulated to be important for spontaneous motor activity and antipsychotic effect of neuroleptics (7-9). These reports suggest that TRH may have some neuroregulatory role in spontaneous motor activity or emotional activity in addition to the role of releasing hormone. The evidence in our previous study indicated that a significant spontaneous motor

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“…Initial studies have suggested that frontal cortical DA has a role opposite to its counterpart in mesolimbic or extrapyramidal DA areas (Carter and Pycock, 1978), where DA-dependent hyperactivity and stereotypy are believed to be mediated (Costall et al, 1977). The inhibitory role initially ascribed to frontal cortical DA stemmed from 6-hydroxydopamine (6-OHDA) studies demonstrating that frontal cortical DA depletion produced hyperactivity after a period of 7-10 d (Pycock et al, 1980a;Robinson and Stitt, 1981;Joyce et al, 1983).…”

mentioning

confidence: 99%

Circling behavior following unilateral microinjections of cocaine into the medial prefrontal cortex: dopaminergic or local anesthetic effect?

Morency¹,

Stewart²,

Beninger³

1987

J. Neurosci.

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Dopaminergic projections to the medial prefrontal cortex have been implicated in cocaine reinforcement; therefore, it was of interest to examine the locomotor effects of acute administration of cocaine to this area. Circling behavior was assessed following injections of 1.0 microliter of cocaine in doses of 0 (0.9% saline), 25, 50, and 100 micrograms/microliters into the medial prefrontal cortex of rats prepared with chronic unilateral guide cannulae. Animals were scored during four 5 min intervals of a 60 min test session that began with the central injection and placement in a flat circular arena. Cocaine was found to produce dose-dependent contraversive circling, an effect previously seen with the dopamine (DA) agonists LY 14 1865 and (+)- amphetamine, suggesting a unilateral stimulant effect. However, since cocaine has potent local anesthetic properties that have been reported to produce behavioral effects and also to inhibit the reuptake of norepinephrine and 5-HT, it was important to demonstrate that the directional bias was a dopaminergic effect. Intra-frontocortical microinjections of the local anesthetic procaine (10, 100, and 1000 micrograms in 0.5 microliter) did not induce circling. Sulpiride (0.001–10.0 micrograms in 0.5 microliter), a DA antagonist specific for the D- 2 receptors, produced ipsiversive circling in a dose-dependent manner in rats treated with (+)-amphetamine (1.5 mg/kg, i.p.). In addition, sulpiride (1.0 micrograms in 0.5 microliter) blocked the circling behavior induced by cocaine (50 micrograms in 0.5 microliter) when administered into the medial prefrontal cortex 15 min prior to the cocaine injection. These results provide further evidence for an excitatory influence of mesocortical DA on motor control.

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Stereotyped behaviour patterns and hyperactivity induced by amphetamine and apomorphine after discrete 6-hydroxydopamine lesions of extrapyramidal and mesolimbic nuclei

Cited by 217 publications

References 47 publications

Birth Insult Alters Dopamine-Mediated Behavior in a Precocial Species, the Guinea Pig Implications for Schizophrenia

Birth Insult Alters Dopamine-Mediated Behavior in a Precocial Species, the Guinea Pig Implications for Schizophrenia

Thyrotropin-releasing rormone: hyperactivity and mesolimbic dopamine system in rats

Circling behavior following unilateral microinjections of cocaine into the medial prefrontal cortex: dopaminergic or local anesthetic effect?

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