The Journal of Neuroscience, April 15, 2002, 22(8):3244-3250
The Rate of Intravenous Cocaine Administration Determines
Susceptibility to Sensitization
Anne-Noël
Samaha,
Yilin
Li, and
Terry E.
Robinson
Department of Psychology (Biopsychology Program), The University of
Michigan, Ann Arbor, Michigan 48109-1109
The potential for addiction is thought to be greatest when drugs of
abuse reach the brain rapidly, because this produces intense subjective
pleasurable effects. However, the ability of drugs to induce forms of
cellular plasticity related to behavioral sensitization may also
contribute to addiction. Therefore, we studied the influence of rate of
intravenous cocaine delivery on its ability to induce psychomotor
sensitization. In one experiment, rotational behavior in rats with a
unilateral 6-hydroxydopamine lesion was used as an index of psychomotor
activation, and in a second experiment, locomotor activity in
neurologically intact rats was used. Rapid (5-16 sec) intravenous
infusions of cocaine induced robust psychomotor sensitization at all
doses tested (0.5-2.0 mg/kg). Treatments given over 25 sec failed to
induce sensitization at all doses tested. Treatments given over 50 or
100 sec induced sensitization only at the highest dose tested. Thus,
the rate of intravenous cocaine delivery has profound effects on the
ability of cocaine to induce psychomotor sensitization. This suggests
that the temporal dynamics of drug delivery to the brain is a critical
factor in the ability of cocaine to induce forms of neuronal plasticity that may contribute to addiction.
Key words:
cocaine; psychomotor sensitization; behavioral
sensitization; intravenous; rate of infusion; 6-hydroxydopamine lesion; rat
Copyright © 2002 Society for Neuroscience 0270-6474/02/2283244-07$05.00/0