title: Rats showing low and high sensitization of frequency-modulated 50-kHz vocalization response to amphetamine differ in amphetamine-induced brain Fos expression.
abstract: Individuals predisposed to addiction constitute a minority of drug users, in both humans and animal models of the disorder, but there are no established characteristics that would allow identifying them beforehand. Our studies demonstrate that sensitization of rat 50-kHz ultrasonic vocalization (USV) response to amphetamine shows marked inter-individual diversity but substantial intra-individual stability. Low sensitization of the response shows relevance to the acquisition of self-administration of this drug and hence might be of predictive value regarding the risk of addiction. We compared amphetamine-induced Fos expression in 16 brain regions considered important for the development of addiction between rats preselected for low and high sensitization of the response and next given nine daily amphetamine doses followed by a 2-week withdrawal and final amphetamine challenge. Ventral tegmental area and nucleus accumbens shell Fos-positive nuclei counts correlated positively with 50-kHz USV response to the challenge in high-sensitized rats. Compared to those in amphetamine-untreated controls, Fos-positive nuclei counts were significantly and markedly (2-6 times) higher in 12 regions in high-sensitized rats, whereas in low-sensitized rats they were significantly higher in the cingulate cortex and dorsomedial striatum only. The difference in the counts between the latter two subsets reached statistical significance in dorsomedial and dorsolateral striatum and three out of four cortical regions studied. The fact that the diversification was most distinct in dorsal striatum that plays a critical role in the transition from controlled to compulsive drug intake suggests that the USV-based categorization may be related to divergent vulnerability of rats to AMPH addiction.
authors: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957 Warsaw, Poland.
authors: Ewelina
authors: E
authors: Kaniuga
authors: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957 Warsaw, Poland. Electronic address: taracha@ipin.edu.pl.
authors: Ewa
authors: E
authors: Taracha
authors: Department of Neuropathology, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957 Warsaw, Poland.
authors: Tomasz
authors: T
authors: Stępień
authors: Department of Neuropathology, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957 Warsaw, Poland.
authors: Teresa
authors: T
authors: Wierzba-Bobrowicz
authors: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957 Warsaw, Poland; Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, 26/28 Krakowskie Przedmieście St., 00-927 Warsaw, Poland.
authors: Adam
authors: A
authors: Płaźnik
authors: Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., 02-106 Warsaw, Poland.
authors: Stanisław J
authors: SJ
authors: Chrapusta
mesh_terms: D000661:Amphetamine / Q000008:administration & dosage*; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017557:Ventral Tegmental Area / Q000187:drug effects / Q000378:metabolism; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D000661:Amphetamine
keywords: Amphetamine; Fos protein; Individual differences; Sensitization; Ultrasonic vocalization