Behavioural sensitisation to repeated d-amphetamine: Effects of excitotoxic lesions of the pedunculopontine tegmental nucleus

Behavioural sensitisation to repeated d-amphetamine: Effects of excitotoxic lesions of the pedunculopontine tegmental nucleus

The pedunculopontine tegmental nucleus (PPTg) interacts with anatomical systems thought to be involved in mediating sensitisation of the locomotor response to repeated d-amphetamine. The PPTg has direct and indirect connections with the nucleus accumbens and prefrontal cortex, and also influences mi...

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Bibliographic Details
Published in:Neuroscience Vol. 118; no. 2; pp. 311 - 315
Main Authors: ALDERSON, H. L, FAULCONBRIDGE, L. F. H, GREGORY, L. P, LATIMER, M. P, WINN, P
Format: Journal Article
Language:English
Published: Oxford Elsevier 01-01-2003
Subjects:
Amphetamine - pharmacology
Animals
Behavior, Animal - drug effects
Biological and medical sciences
Brain Mapping
Central Nervous System Stimulants - pharmacology
Drug addictions
Locomotion - drug effects
Male
Medical sciences
Neurotoxins - adverse effects
Rats
Tegmentum Mesencephali - drug effects
Tegmentum Mesencephali - physiology
Toxicology
Dopamine
Rat
Toxicity
mesopontine
Rodentia
Central nervous system
Tegmental nucleus
corticostriatal
Vertebrata
Mammalia
Animal
Excitotoxicity
Neurotransmitter
Amfetamine
Acetylcholine
Sensitization
Drug of abuse
Lesion
Brain (vertebrata)
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Summary:The pedunculopontine tegmental nucleus (PPTg) interacts with anatomical systems thought to be involved in mediating sensitisation of the locomotor response to repeated d-amphetamine. The PPTg has direct and indirect connections with the nucleus accumbens and prefrontal cortex, and also influences midbrain dopamine activity through direct projections to substantia nigra and ventral tegmental area. In this experiment, the development of behavioural sensitisation to the locomotor stimulant effects of repeated d-amphetamine was examined in rats bearing excitotoxic lesions of the PPTg, and sham-lesioned controls. Rats were given repeated d-amphetamine (1.5 mg/kg i.p.) treatment in an on-off procedure, with saline and d-amphetamine given on alternate days, such that rats received a total of seven d-amphetamine and seven saline treatments. Locomotor responses were measured in photocell cages. On the first day of d-amphetamine treatment, there was no difference between excitotoxin and sham-lesioned rats. Development of sensitisation to the locomotor stimulant effects of d-amphetamine was delayed in PPTg-lesioned rats, relative to the sham-lesioned control rats. However, there was no difference between lesion and control groups in the locomotion seen on saline-treatment days. These data suggest that the PPTg is involved in the development of behavioural sensitisation to the locomotor stimulant effects of repeated d-amphetamine, and indicate that traditional striatal circuitry models of the mechanisms underlying sensitisation should be extended to include the PPTg.
ISSN:0306-4522
1873-7544
DOI:10.1016/S0306-4522(03)00152-0