R. Kuczenski et Ds. Segal, Dynamic changes in sensitivity occur during the acute response to cocaine and methylphenidate, PSYCHOPHAR, 147(1), 1999, pp. 96-103
Rationale: We have previously shown that during the acute response to amphe
tamine, a stimulant that released dopamine, behavioral sensitivity to the d
rug undergoes dynamic changes, as evident in the altered behavioral profile
expressed to the subsequent administration of a low dose of the drug. Obje
ctive: The present studies were designed to determine if these dynamic chan
ges in sensitivity occur with amphetamine-like stimulants that act primaril
y by blocking dopamine uptake. Methods: Groups of animals were primed with
40 mg/kg cocaine or 30 mg/kg methylphenidate, then during the acute respons
e, a low, locomotor-stimulant dose of amphetamine (1.5 mg/kg) was administe
red to probe for changes in sensitivity. Conversely, to determine whether t
he manifestation of the increased responsivity is idiosyncratic to amphetam
ine, animals were also primed with amphetamine (4 mg/kg), then probed with
low doses of cocaine (10 and 20 mg/kg) or methylphenidate (10 mg/kg). Paral
lel microdialysis studies were performed to assess the caudate-putamen and
nucleus accumbens extracellular dopamine responses. Results: Priming with t
he uptake blockers each resulted in a stereotypy response to the subsequent
low-dose amphetamine probe. Likewise, after priming with amphetamine, the
uptake blockers each induced a pronounced stereotypy response. In each case
, these changes in behavioral responsivity were expressed in the absence of
corresponding changes in the probe-induced regional dopamine responses. Co
nclusions: Dynamic changes in behavioral sensitivity during the response to
acute stimulant administration are a characteristic common to both dopamin
e releasers and uptake blockers. These rapid changes in sensitivity may con
tribute to the behaviors associated with binge patterns of drug abuse.