title: Poor sensitization of 50-kHz vocalization response to amphetamine predicts rat susceptibility to self-administration of the drug.
abstract: Our previous studies showed promise for using sensitization of the frequency-modulated 50-kHz vocalization response to amphetamine (AMPH) as an index of rat vulnerability to AMPH addiction.
  
  
  
  This study aimed to test the utility of sensitizing frequency-modulated (FM) 50-kHz vocalization in the AMPH self-administration paradigm as well as the ability of N-acetylcysteine to prevent self-administration relapse.
  
  
  
  Rats were subjected to the so-called two-injection protocol of sensitization (TIPS) using AMPH and were categorized as low-sensitized callers (LCTIPS) or high-sensitized callers (HCTIPS) based on the individual outcomes. Then, they were given 44 sessions of AMPH self-administration followed by a 17-session N-acetylcysteine-aided extinction course and a single session of AMPH-primed self-administration reinstatement.
  
  
  
  LCTIPS compared to HCTIPS rats showed no considerable difference in the FM 50-kHz vocalization rate during the self-administration training or extinction course, but they were considerably more likely to acquire AMPH self-administration and experience drug-induced reinstatement of this trait. Moreover, the LCTIPS rats were more likely than HCTIPS rats to have a markedly higher FM 50-kHz vocalization rate after AMPH reinstatement. N-acetylcysteine did not affect the course of self-administration extinction or the instrumental or FM 50-kHz vocalization responses to AMPH reinstatement.
  
  
  
  There is no link between the FM 50-kHz vocalization and key characteristics of AMPH self-administration. Additionally, N-acetylcysteine does not help prevent AMPH self-administration relapse. However, there is a high predictive value for poor sensitization of the FM 50-kHz vocalization response to AMPH with respect to the acquisition and maintenance of self-administration of this psychostimulant.
authors.affiliation: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957, Warsaw, Poland. taracha@ipin.edu.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Taracha
authors.affiliation: Department of Neurochemistry, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957, Warsaw, Poland.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Kaniuga
authors.affiliation: Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957, Warsaw, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Wyszogrodzka
authors.affiliation: 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.forename: Adam
authors.initials: A
authors.lastname: Płaźnik
authors.affiliation: Department of Pharmacology and Physiology of the Nervous System, Institute of Psychiatry and Neurology, 9 Sobieskiego St., 02-957, Warsaw, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Stefański
authors.affiliation: Department of Experimental Pharmacology, Mossakowski Medical Research Centre, Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland.
authors.forename: Stanisław J
authors.initials: SJ
authors.lastname: Chrapusta
mesh_terms: D000111:Acetylcysteine / Q000494:pharmacology; D000661:Amphetamine / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration; D014828:Vocalization, Animal / Q000187:drug effects*
chemical_list: D000697:Central Nervous System Stimulants; D016166:Free Radical Scavengers; D000661:Amphetamine; D000111:Acetylcysteine
keywords: Addiction; Affective state; Amphetamine self-administration; Drug context; Drug dependence; Individual differences; Instrumental response; N-acetylcysteine; Sensitization; Ultrasonic vocalization