An activity indicator of acute withdrawal depends on amphetamine dose in rats.
A moderate dose of amphetamine (AMPH) produces hypoactivity around 20 h post-administration. This hypoactivity may be an indicator of an acute withdrawal state. The purpose was to see how AMPH doses affected the expression of this hypoactivity and, by inference, AMPH-induced acute withdrawal. Rats were housed in individual open fields, with free access to food and water. Light-dark cycles were scheduled such that drug-elicited patterns could be readily detected. Animals first received a series of eight control treatments, and then a series of 10 experimental treatments spaced at 33-h intervals. Different experimental treatment groups received saline, 1.0 mg/kg, 2.0 mg/kg, or 4.0 mg/kg AMPH. The effects of these treatments on 33-h patterns of locomotor activity were observed. Control treatments produced no systematic time-dependent changes in activity beyond the first hour post-treatment. All doses of AMPH produced typical short-term effects: They markedly increased locomotion and/or stereotypy during the first 3 to 6 h post-treatment. Acute and chronic administrations of the 2.0 and 4.0 mg/kg doses also produced similar changes in longer term activity patterns: They produced hypoactivity 20 h later, followed by a recovery of activity around hour 25 post-treatment. The timing of amphetamine-induced hypoactivity and acute withdrawal may be independent of dose over a wide range of doses. Time-dependent changes in AMPH-induced state may influence motivation and drug-related assessments. The methodology described here may provide an easy and rapid way to investigate the determinants of AMPH-induced hypoactivity and acute withdrawal.
White
Wesley
W
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zürich (ETHZ), Schwerzenbach, CH-8603, Switzerland. w.white@moreheadstate.edu
White
Ilsun M
IM
D000661:Amphetamine / Q000008:administration & dosage* / Q000009:adverse effects*; D000818:Animals; D000697:Central Nervous System Stimulants / Q000008:administration & dosage* / Q000009:adverse effects*; D002940:Circadian Rhythm; D003624:Darkness; D004305:Dose-Response Relationship, Drug; D008027:Light; D008297:Male; D009042:Motivation; D009043:Motor Activity / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013239:Stereotyped Behavior / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D013997:Time Factors
D000697:Central Nervous System Stimulants; D000661:Amphetamine