The pharmacological and anatomical substrates of the amphetamine response in the rat
Abstract
Bilateral 6-hydroxydopamine microinjections into the substantia nigra abolished both the locomotor and stereotyped responses to d-amphetamine in adult rats. The lesions resulted in a depletion of over 99 per cent of striatal tyrosine hydroxylase activity (indicating a near total lesion of the nigro-striatal dopamine pathway) as well as severe noradrenaline depletions. However, lesion of the dorsal or ventral noradrenergic pathways resulted in similar noradrenaline depletions but with no effect on striatal tyrosine hydroxylase levels and without the concomitant blockage of the amphetamine response. The substantia nigra lesioned rats were behaviourally supersensitive to apomorphine and L-DOPA and did not show a locomotor response to cocaine. The substantia nigra lesioned rats were not aphagic or adipsic. It was concluded that both the locomotor and stereotyped responses induced by amphetamine are dependent on the functional integrity of the nigro-striatal dopamine pathway.
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Both novelty-induced locomotor activity and the hyperactivity evoked by amphetamine depend on nucleus accumbens dopamine neurotransmission.
“Given that both novelty-induced locomotor activity (Hooks and Kalivas 1994) and the hyperactivity evoked by amphetamine depend on nucleus accumbens dopamine neurotransmission (Creese and Iversen 1975; Pijnenburg et al. 1975)”
From Neurexin1α knockout in rats causes aberrant social behaviour: relevance for autism and schizophrenia (2025) · cites this paper as Creese and Iversen 1975
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“…locomotor activity (Hooks and Kalivas 1994) and the hyperactivity evoked by amphetamine depend on nucleus accumbens dopamine neurotransmission (Creese and Iversen 1975; Pijnenburg et al. 1975), these findings suggest that nucleus accumbens dopaminergic neurotransmission is hypersensitive in…”
- Authors
- Creese, I., & Iversen, S. D.
- Affiliations
- University of Cambridge (GB)
- Venue
- Brain Research
- Publisher
- Elsevier BV
- Published
- 1975-01
- Volume
- 83
- Issue
- 3
- Pages
- 419-436
- ISSN
- 0006-8993 (ISSN-L)
- OpenAlex
- W2092998813
- Cited by
- 583
- References
- 0
- Citations by year
- 2025: 1 · 2024: 3 · 2023: 2 · 2021: 3 · 2020: 2 · 2019: 2 · 2018: 4 · 2017: 4 · 2016: 4 · 2015: 5 · 2014: 6 · 2013: 10 · 2012: 5
- FWCI
- 14.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Brain Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Medical Research Council
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Health Sciences › Medicine › Neurology › Parkinson's Disease Mechanisms and Treatments
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- amphetamine, substantia nigra, 6-hydroxydopamine lesion, norepinephrine depletion, noradrenergic pathways, locomotor response, stereotypy, L-DOPA, cocaine, dopamine
- MeSH terms
- Animals, Apomorphine, Behavior, Animal, Body Weight, Cerebral Cortex, Cocaine, Dextroamphetamine, Drinking Behavior, Feeding Behavior, Humans, Hydroxydopamines, Levodopa, Locomotion, Male, Neural Pathways, Norepinephrine, Receptors, Adrenergic, Stereotyped Behavior, Stimulation, Chemical, Substantia Nigra, Tyrosine 3-Monooxygenase, Rats
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