St. Cunningham et al., SENSITIZATION OF THE LOCOMOTOR RESPONSE TO PSYCHOSTIMULANTS AFTER REPEATED OPIATE EXPOSURE - ROLE OF THE NUCLEUS-ACCUMBENS, Neuropsychopharmacology, 16(2), 1997, pp. 147-155
The following experiments were performed to ascertain the role of the
nucleus accumbens in opiate-dopamine interactions using measures of lo
comotor activity. Three separate experiments were carried out. In Expe
riment 1, rats received systemic morphine (10 mg/kg IP) or saline (1 m
l/kg IP) every other day for 5 days, followed by systemic amphetamine
(1.5 mg/kg) 48 hours following the fifth injection. Animals in the mor
phine pretreatment group exhibited a sensitized locomotor response to
amphetamine. In Experiment 2, animals received the same systemic pretr
eatment and were subsequently given intraaccumbens saline, amphetamine
(2.5 mu g/0.5 mu l) or cocaine (7 mu g/0.5 mu l), each separated by 4
8 hours. Morphine-pretreated animals showed enhanced motor activity in
response to intraaccumbens microinfusion of the psychostimulant drugs
. Finally, in Experiment 3, multiple microinjections of morphine (0.5
mu g/0.5 mu l) directly into the nucleus accumbens resulted in a poten
tiated locomotor response to intraaccumbens amphetamine (2.5 mu g/0.5
mu l). These data indicate that the nucleus accumbens may contribute t
o both the development and expression of opiate-stimulant cross-sensit
ization. The neural basis of this sensitization is hypothesized to be
a common intracellular pathway affected by both classes of drugs, such
as the cyclic adenosine monophosphate (AMP) system. (C) 1997 American
College of Neuropsychopharmacology [Neuropsychopharmacology 16:147-15
5, 1997]