RationaleOur 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.ObjectiveThis 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.MethodsRats 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.ResultsLCTIPS 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.ConclusionsThere 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.
Measurement of hair drug content may be a reliable biomarker of the history of drug exposure, allowing to assess patient long‐term compliance. Studies on correlations between antiepileptic drugs intake and their hair contents are limited. The aim of the study was to determine the association between the history of levetiracetam administration and its content in rat hair in controlled laboratory conditions. Additionally, the effects of levetiracetam on hair growth rate and body‐weights were examined. Three groups of 12 rats each were exposed to different schedules of levetiracetam administration (10 mg/kg i.p.: every 24, 48 and 72 hours) for 30 days. The control group received daily saline injection. Levetiracetam concentrations in hair were assessed by validated LC‐MS/MS method. The mean hair concentrations were as follows: 300 (±100), 170 (±60) and 130 (±80) ng/mg for rats receiving levetiracetam every 24, 48 and 72 hours, respectively. The levetiracetam accumulation in the hair was correlated with the total number of doses received (r = .699, P < .001). Levetiracetam did not affect the hair growth rate and rat body‐weight. The concentration of levetiracetam measured in rat hair represents a reliable marker. It may reflect the adherence to levetiracetam treatment; however, further studies on human beings are needed.
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