Repeated amphetamine administration in rats revealed consistency across days and a complete dissociation between locomotor and hypothalamic-pituitary-adrenal axis effects of the drug.
BACKGROUND
Most drugs of abuse stimulate both locomotor activity and the hypothalamic-pituitary-adrenal (HPA) axis, but the relationship between the two responses within the same subjects and their reliabilities has been scarcely studied. Our objectives were to study: (1) the consistency and stability across time of locomotor and HPA activation induced by repeated d-amphetamine (AMPH); (2) the relationship between locomotor and hormonal responses to AMPH; and (3) the relationship between novelty-induced activity and both types of responses to the drug.


METHODS
Male adult rats were exposed to a novel environment to study the locomotor response. Later, they were injected with AMPH (2 mg/kg, sc) for 5 days. In Experiment 1, Plasma adrenocorticotropin (ACTH) and corticosterone levels in response to AMPH were studied on days 1, 3, and 5, and locomotor response on days 2 and 4. In Experiment 2, ACTH and corticosterone responses were studied on days 2 and 4, and locomotor response on days 1, 3, and 5.


RESULTS
Across days, both locomotor and HPA responses to the drug were consistent, but independent measures, unrelated to the reactivity to novelty. As measured by the area under the curve, the HPA response to AMPH desensitized with the repeated injection, whereas the initial locomotor response to the drug increased.


CONCLUSIONS
Dissociation exists between HPA and locomotor activation induced by AMPH, which seemed to be both reliable individual traits. Locomotor reactivity to novelty was related neither to HPA nor to locomotor responses to AMPH.
Gagliano
Humberto
H
Institute of Neurosciences, Autonomous University of Barcelona, Bellaterra, Barcelona, Spain.
Andero
Raül
R
Armario
Antonio
A
Nadal
Roser
R
D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D019540:Area Under Curve; D000697:Central Nervous System Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D003345:Corticosterone / Q000097:blood; D003913:Dextroamphetamine / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004777:Environment; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects*; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
D000697:Central Nervous System Stimulants; D000324:Adrenocorticotropic Hormone; D003913:Dextroamphetamine; D003345:Corticosterone