Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core.
BACKGROUND
Repeated exposure to psychostimulant drugs causes a long-lasting increase in the psychomotor and reinforcing effects of these drugs and an array of neuroadaptations. One such alteration is a hypersensitivity of striatal activity such that a low dose of amphetamine in sensitized animals produces dorsal striatal activation patterns similar to acute treatment with a high dose of amphetamine.


OBJECTIVE
To extend previous findings of striatal hypersensitivity with behavioral observations and with cellular activity in the nucleus accumbens and prefrontal cortex in sensitized animals.


METHODS
Rats treated acutely with 0, 1, 2.5, or 5 mg/kg i.p. amphetamine and sensitized rats challenged with 1 mg/kg i.p. amphetamine were scored for stereotypy, rearing, and grooming, and locomotor activity recorded. c-fos positive nuclei were quantified in the nucleus accumbens and prefrontal cortex after expression of sensitization with 1 mg/kg i.p. amphetamine.


RESULTS
Intense stereotypy was seen in animals treated acutely with 5 mg/kg amphetamine, but not in the sensitized group treated with 1 mg/kg amphetamine. The c-fos response to amphetamine in the accumbens core was augmented in amphetamine-pretreated animals with a shift in the distribution of optical density, while no effect of sensitization was seen in the nucleus accumbens shell or prefrontal cortex.


CONCLUSIONS
A lack of stereotypy in the sensitized group indicates a dissociation of behavioral responses to amphetamine and striatal immediate-early gene activation patterns. The increase in c-fos positive nuclei and shift in the distribution of optical density observed in the nucleus accumbens core suggests recruitment of a new population of neurons during expression of sensitization.
Nordquist
R E
RE
Department of Anatomy and Neurosciences, Vrije Universiteit Medical Center, Amsterdam, The Netherlands. r.e.nordquist@uu.nl
Vanderschuren
L J M J
LJ
Jonker
A J
AJ
Bergsma
M
M
de Vries
T J
TJ
Pennartz
C M A
CM
Voorn
P
P
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D016762:Genes, fos / Q000187:drug effects; D006120:Grooming / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009714:Nucleus Accumbens / Q000166:cytology* / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000166:cytology / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011999:Recruitment, Neurophysiological / Q000187:drug effects*; D013239:Stereotyped Behavior / Q000187:drug effects
D000697:Central Nervous System Stimulants; D000661:Amphetamine