Expression of amphetamine sensitization is associated with recruitment of a reactive neuronal population in the nucleus accumbens core

• Published in: Psychopharmacologia Vol. 198; no. 1; pp. 113 - 126
• Main Authors: Nordquist, R. E., Vanderschuren, L. J. M. J., Jonker, A. J., Bergsma, M., de Vries, T. J., Pennartz, C. M. A., Voorn, P.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.05.2008; Springer; Springer Nature B.V
• Subjects: Amphetamine - pharmacology; Amphetamines; Animal behavior; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Brain research; Central Nervous System Stimulants - pharmacology; Dose-Response Relationship, Drug; Gene expression; Genes, fos - drug effects; Grooming - drug effects; Immunohistochemistry; Male; Medical sciences; Motor Activity - drug effects; Neurons; Neurons - drug effects; Neuropharmacology; Neurosciences; Neurotransmitters; Nucleus Accumbens - cytology; Nucleus Accumbens - drug effects; Original Investigation; Pharmacology. Drug treatments; Pharmacology/Toxicology; Prefrontal Cortex - cytology; Prefrontal Cortex - drug effects; Psychiatry; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer; Psychoanaleptics: cns stimulant, antidepressant agent, nootropic agent, mood stabilizer..., (alzheimer disease); Psychology. Psychoanalysis. Psychiatry; Psychopharmacology; Rats; Rats, Wistar; Recruitment, Neurophysiological - drug effects; Rodents; Stereotyped Behavior - drug effects; Locomotion; Striatum; Prefrontal cortex; Behavioral sensitization; Immediate-early gene; Stereotypy; Amphetamine derivatives; CNS stimulant; Psychotropic; Central nervous system; Basal ganglion; Corpus striatum; Encephalon; Recruitment; Nucleus accumbens; Amfetamine; Sensitization; Behavior; Immediate early gene
• ISSN: 0033-3158; 1432-2072
• DOI: 10.1007/s00213-008-1100-4

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