Differentiation of the dopamine mechanisms mediating stereotyped behaviour and hyperactivity in the nucleus accumbens and caudate-putamen

Costall, B.; Naylor, R.J.; Cannon, Joseph G.; Lee, Theresa

doi:10.1111/j.2042-7158.1977.tb11331.x

Cited by 173 publications

(31 citation statements)

References 15 publications

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“…High doses of apomorphine injected into the nucleus accumbens resulted in hyperlocomotion without affecting sniffing behavior, while similar injections into the nucleus caudatus induced stereotyped sniffing without changing the locomotor activity of the animals. This agrees well with the purported role of the mesolimbic and nigro-striatal dopaminergic systems with projections to the nucleus accumbens and nucleus caudatus respectively in the apomorphine-induced hyperactivity and stereotypy respectively (17)(18)(19)(20).…”

Section: Discussionsupporting

confidence: 89%

γ-endorphin and Nα-acetyl-γ-endorphin interfere with distinct dopaminergic systems in the nucleus accumbens via opioid and non-opioid mechanisms

1984

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SummaryLow doses (10 ng) of the dopamine agonist apomorphine induced hypolocomotion when injected into the nucleus accumbens of rats. This behavioral response was antagonized by local treatment with either the opioid peptide 7-endorphin (yE) or the non-opioid peptide N aacetyl-y-endorphin (AcyE) in a dose of 100 pg. High doses of apomorphine (10 ug) or amphetamine (2 ug) injected into the nucleus accumbens resulted in hyperlocomotion. This response was blocked by pretreatment with yE but not with AcyE. This effect of yE could be prevented by local treatment with naloxone. Neither peptides interfered with the apomorphine-induced stereotyped sniffing when the substances were injected into the nucleus caudatus. It is concluded that yE and AcyE differentially interact with distinct dopaminergic systems in the nucleus accumbens of the rat brain via an opioid and a non-opioid mechanism, suggesting that the peptide fragments originating from pro-opiomelanocortin may be specifically implicated in the control of dopaminergic activity in this brain area.The opioid peptide y-endorphin (yE) produces behavioral effects in rats which resemble those of neuroleptics in certain aspects (I-3). This neurolepticlike action can also be elicited by fragments of yE i.c. des-Tyr1-y-endorphin (DTyE) and desenkephalin-y-endorphin (DEyE), that are devoid of opiate activity (1,4-6). Thus, the opiate and neuroleptic-like action of yE may be mediated by distinct brain mechanisms. Research in this respect is especially focussed on brain dopamine (6-9), since neuroleptic drugs are potent blockers of dopaminergic activity (10), and opioid peptides have been implicated in the control of certain dopaminergic systems in the brain (11). Previously, we have reported that following subcutaneous administration DTyE and DEyE antagonized the hypolocomotion induced by low doses of the dopamine agonist apomorphine, while these peptides did not interfere with the hyperlocomotion and stereotyped behavior elicited by high doses of apomorphine (6,12). Subsequently, it was found that low doses of apomorphine injected directly into the nucleus accumbens resulted in hypolocomotion (13). This behavioral resonse was antagonized by pretreatment with DTyE and DEyE (7). High doses of apomorphine injected into the nucleus accumbens produced hyperlocomotion. This response was not affected by pretreatment with DEyE (14). From these studies it was concluded that ytype endorphins interfere with certain, but not all, dopaminergic systems in the nucleus accumbens.Recently, N -acetyl-y-endorphzn (AcyE) has been isolated from pituitary

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Section: Discussionsupporting

confidence: 89%

γ-endorphin and Nα-acetyl-γ-endorphin interfere with distinct dopaminergic systems in the nucleus accumbens via opioid and non-opioid mechanisms

1984

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“…This agrees well with the purported role of the nigrostriatal and mesolimbic dopaminergic systems in the apomorphine-induced stereotypy and hyperactivity respectively (Kelly et al, 1975;Kelly and Iversen, 1976;Pijnenburg et al, 1975;Costall et al, 1977). The stimulant effect of a high dose of apomorphine is attributed to activation of postsynaptic DA receptors in the CNS (Andrn et al, 1967).…”

Section: Discussionsupporting

confidence: 88%

The hypomotility elicited by small doses of apomorphine seems exclusively mediated by dopaminergic systems in the nucleus accumbens

Radhakishun

Ree

1987

European Journal of Pharmacology

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The reduction of motor activity elicited in rats by a subcutaneous injection of a small dose of apomorphine was reversed by pretreatment of the nucleus accumbens with haloperidol (10 pg), sulpiride (10 pg) or desenkephalin--f-endorphin (DE),E) (100 pg or 10 ng). These doses of the compounds did not change motor activity in placebo-treated rats. Pretreatment of the nucleus caudatus with the same neuroleptics or DE'rE did not diminish the effect of subcutaneously administered low doses of apomorphine. A small dose of apomorphine decreased motor activity when it was injected directly into the nucleus accumbens. This effect was dose dependently antagonized by subcutaneous pretreatment with DE~,E. It is suggested that the hypoactivity elicited by small doses of apomorphine is exclusively mediated by dopaminergic systems in the nucleus accumbens.

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“…These models include antagonism (EDSo = 0.095 mg/kg i. p.) of apomorphine-induced climbing behavior in mice (CMA; 26,27) and antagonism of avoidance responding in a discrete trial signaled avoidance paradigm, namely, pole climb avoidance in rats (26,47). Iloperidone demonstrates an antipsychotic-like selective inhibition of avoidance responding at doses that do not suppress escape respond- (47).…”

Section: Positive Symptomsmentioning

confidence: 99%

Iloperidone: Preclinical Profile and Early Clinical Evaluation

Corbett¹,

Griffiths²,

Shipley³

et al. 1997

CNS Drug Reviews

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Differentiation of the dopamine mechanisms mediating stereotyped behaviour and hyperactivity in the nucleus accumbens and caudate-putamen

Cited by 173 publications

References 15 publications

γ-endorphin and Nα-acetyl-γ-endorphin interfere with distinct dopaminergic systems in the nucleus accumbens via opioid and non-opioid mechanisms

γ-endorphin and Nα-acetyl-γ-endorphin interfere with distinct dopaminergic systems in the nucleus accumbens via opioid and non-opioid mechanisms

The hypomotility elicited by small doses of apomorphine seems exclusively mediated by dopaminergic systems in the nucleus accumbens

Iloperidone: Preclinical Profile and Early Clinical Evaluation

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