Ds. Segal et R. Kuczenski, Escalating dose-binge treatment with methylphenidate: Role of serotonin inthe emergent behavioral profile, J PHARM EXP, 291(1), 1999, pp. 19-30
Citations number
54
Categorie Soggetti
Pharmacology & Toxicology
Journal title
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
Our previous studies indicate that exposure of rats to an escalating-dose,
multibinge pattern of amphetamine or methamphetamine administration results
in a unique emergent behavioral profile and concomitant regionally specifi
c dopamine response patterns in the nucleus accumbens and caudate-putamen.
In the present study, we explored the generality of these effects by using
an escalating-dose, multibinge treatment with methylphenidate (MP), a stimu
lant that, unlike the amphetamines, produces no increase in serotonin trans
mission. Furthermore, MP exerts many of its effects through dopamine uptake
blockade, in contrast to the amphetamines that primarily release dopamine.
The results showed that MP administered according to an escalating-dose, m
ultibinge regimen produced the expression of the emergent behavioral profil
e. This pattern of behavior was also evident in these animals in response t
o 2.5 mg/kg acute amphetamine after the last MP binge exposure. Consistent
with previous evidence, neither acute nor multibinge MP treatment produced
a significant serotonin response. In contrast, a regionally specific dopami
ne response alteration was observed during the course of this treatment. Ca
udate-putamen dopamine exhibited a pattern of increasing response during an
acute MP binge but pronounced tolerance developed to this effect after mul
tiple binges. By contrast, the nucleus accumbens dopamine response did not
significantly change during the acute binge and exhibited a slight incremen
tal pattern to the injections of the final binge. These findings, along wit
h the effects of other stimulants, are discussed in terms of a possible rol
e for serotonin and for the differential changes in the caudate-putamen and
nucleus accumbens dopamine responses in the emergent behavioral profile. T
he similarity between the effects of MP and the amphetamines provides furth
er support for the multibinge-induced behavioral profile as a possible anim
al model for stimulant-induced psychosis.