ReviewHigh-anxiety rats are less sensitive to the rewarding affects of amphetamine on 50 kHz USV
Introduction
In rats, as in humans, there are a great deal of individual differences in the responses to stress and behavioural responses to the pharmacological activation of the mesolimbic system [1], [2], [3], [4]. Our previous studies on high-anxiety rats (HR) and low-anxiety rats (LR), which were selected based on their behaviour in the contextual fear test (i.e., the duration of the freezing response was used as the discriminating variable), showed that HR rats were characterised by an anxiogenic and depressive-like phenotype, using a passive coping strategy, showing decreased activity in the prefrontal cortex and increased activity in the basolateral amygdala (as shown in c-Fos studies) compared with the LR group. In contrast, LR rats were characterised by an active coping strategy, less anxiogenic and depressive-resilience behaviour, and increased activity of the prefrontal cortex and the dentate gyrus (DG) of the hippocampus [5], [6], [7].
It is well documented that dopaminergic transmission in the mesolimbic system is important for information processing, emotional responses to environmental changes, and strategies for coping with stress [8], [9], [10], [11]. Dopamine plays a critical role in the detection of novel information, which is essential for the consolidation, storage and retrieval of memories, all of which are likely to be impaired in depressed patients [11], [12]. Finally, it should be emphasised that dopamine is considered to be the main neurotransmitter involved in the mediation of different natural and drug-induced positive reinforcements [13], [14], [15], [16].
The frequency-modulated 50 kHz ultrasonic calls (FM 50 kHz, USV) offer a valuable index of the positive affective states evoked by naturally rewarding stimuli (e.g., food, social contacts) and induced by some psychostimulants (e.g., amphetamine) [17], [18], [19], [20], [21], [22].
It is hypothesised that differences in dopaminergic activity may be one of the biological factors underlying individual differences in emotional responses and behavioural sensitisation to psychostimulants. We examined this interesting issue using behavioural responses measured by FM 50 kHz calls in rats with different fear-conditioned response strengths, either low-anxiety rats (LR) or high-anxiety (HR) rats, after amphetamine injection in a two-injection protocol (TIPS). In rats, repeated exposure to psychostimulant drugs results in a long-lasting enhancement of behavioural response, otherwise known as behavioural sensitisation [23], [24]. TIPS allows an easy distinction between the induction of sensitisation after the first injection and the drug's expression after a second injection, enabling the assessment of the long-lasting effects of a single exposure to drugs [25]. TIPS has been successfully used for the locomotor sensitisation of mice to morphine and cocaine [25]. It was previously shown that assessment of 50 kHz USV recording in TIPS model provides a good paradigm to observe sensitisation to amphetamine [26], [27]. In the literature, there is little information on the role of amygdala in the expression of 50 kHz calls. This fact is particularly interesting given that psychostimulants can produce both positive and aversive effects [28].
Electrophysiological studies have recently found that ultrasonic stimuli applied in two frequency ranges (22 kHz and 50 kHz) produced significant and opposite effects on single-unit responses to these stimuli in the lateral rat amygdala, indicating its contribution to the processing of both ethologically essential social signals [14]. For these reasons, we decided to analyse the role of the prefrontal cortex and basolateral amygdala. We also wanted to determine whether individual predisposition to a stronger fear response influences the development of sensitisation to psychoactive substances. An additional aim of this study was to test a new model of differential susceptibility to psychoactive drugs.
Section snippets
Animals
Male Wistar rats (n = 78, 200–220 g body weight, 8 weeks old at arrival) purchased from the stock of the Centre for Experimental Medicine, Medical University of Białystok, Poland, were housed under standard laboratory conditions with a 12 h light/dark cycle (lights on at 7 a.m.) at a constant temperature (21 ± 2 °C). They had ad libitum access to tap water and standard laboratory rodent chow. The experiments were performed in accordance with the European Communities Council Directive of November 24,
USV data for TIPS evoked changes
The two-way repeated measures ANOVA did not reveal statistically significant differences in FM 50 kHz USV response during pre-amphetamine exposure to the testing box between the HR and LR groups. There was a significant exposure effect [F(1,48) = 5.97, (P < 0.05)], time effect [F(3,144) = 5.66, (P < 0.01)] and time × exposure effect [F(3,144) = 3.81, (P < 0.05)] but no group effect [F(1,48) = 1.46, (P = 0.23)], no group × exposure effect [F(1,40) = 0.89, (P = 0.35)], no time × group effect [F(3,144) = 1.63, (P = 0.18)], and
Discussion
Both groups of rats demonstrated faster behavioural responses, as measured by FM 50 kHz USV calls, after a second injection of amphetamine. However, in response to a second injection of amphetamine, the LR rats showed much more intense FM 50 kHz USV calls than did the HR rats, both 5 and 10 min after drug administration. The LR rats also had a higher baseline concentration of DA and HVA in the amygdala complex and HVA in the prefrontal cortex (‘ex vivo’ study) and a stronger fear-conditioned
Acknowledgments
This study was supported by the Institute of Psychiatry and Neurology in Warsaw, Poland and Grant No. UMO-2011/03/B/NZ4/02385 from the National Science Centre, Poland.
References (54)
- et al.
Expression of c-Fos and CRF in the brains of rats differing in the strength of a fear response
Behav Brain Res
(2008) - et al.
The expression of c-Fos and colocalisation of c-Fos and glucocorticoid receptors in brain structures of low and high anxiety rats subjected to extinction trials and re-learning of a conditioned fear response
Neurobiol Learn Mem
(2009) - et al.
Changes in the brain expression of alpha-2 subunits of the GABA-A receptor after chronic restraint stress in low- and high-anxiety rats
Behav Brain Res
(2013) - et al.
Selective activation of mesoamygdaloid dopamine neurons by conditioned stress: attenuation by diazepam
Brain Res
(1992) - et al.
Amygdalar control of the mesocorticolimbic dopamine system: parallel pathways to motivated behavior
Neurosci Biobehav Rev
(2003) - et al.
The hippocampal-VTA loop: controlling the entry of information into long-term memory
Neuron
(2005) Ethotransmission: communication of emotional states through ultrasonic vocalization in rats
Curr Opin Neurobiol
(2013)- et al.
Positive and negative ultrasonic social signals elicit opposing firing patterns in rat amygdala
Behav Brain Res
(2012) - et al.
Pharmacological characterization of 50-kHz ultrasonic vocalizations in rats: comparison of the effects of different psychoactive drugs and relevance in drug-induced reward
Neuropharmacology
(2012) - et al.
50-kHz calls in rats: effects of MDMA and the 5-HT1A receptor agonist 8-OH-DPAT
Pharmacol Biochem Behav
(2012)
High-frequency ultrasonic vocalizations index conditioned pharmacological reward in rats
Physiol Behav
Positive affective vocalizations during cocaine and sucrose self-administration: a model for spontaneous drug desire in rats
Neuropharmacology
Effects of intraaccumbens amphetamine on production of 50 kHz vocalizations in three lines of selectively bred Long-Evans rats
Behav Brain Res
The neural basis of drug craving: and incentive-sensitization theory of addiction
Brain Res Brain Res Rev
Diverging frequency-modulated 50-kHz vocalization, locomotor activity and conditioned place preference effects in rats given repeated amphetamine treatment
Neuropharmacology
A rodent “self-report” measure of methamphetamine craving? Rats ultrasonic vocalizations during methamphetamine self-administartion, extinction, and reinstatement
Behav Brain Res
Differences in the density of GABA-A receptor alpha-2 subunits and gephyrin in brain structures of rats selected for low and high anxiety in basal and fear-stimulated conditions, in a model of contextual fear conditioning
Neurobiol Learn Mem
Simple method for simultaneous determination of acetylcholine, choline, noradrenaline, dopamine and serotonin in brain tissue by high-performance liquid chromatography with electrochemical detection
J Chromatogr
Novelty-seeking behavior predicts vulnerability in a rodent model of depression
Physiol Behav
Enhancement of delayed release of dopamine in the amygdala induced by conditioned fear stress in methamphetamine-sensitized rats
Eur J Pharmacol
Protein expression profile in the amygdala of rats with methamphetamine-induced behavioral sensitization
Neurosci Lett
Differential effects of inescapable footshocks and of stimuli previously paired with inescapable footshocks on dopamine turnover in cortical and limbic areas of the rat
Life Sci
Classical fear conditioning in functional neuroimaging
Curr Opin Neurobiol
The effect of chronic administration of corticosterone on anxiety- and depression-like behavior and the expression of GABA-A receptor alpha-2 subunits in brain structures of low- and high-anxiety rats
Horm Behav
Factors that predict individual vulnerability to amphetamine self-administration
Science
Predisposition to self-administer amphetamine: the contribution of response to novelty and prior exposure to the drug
Psychopharmacology (Berl)
Social defeat alters the acquisition of cocaine self-administration in rats: role of individual differences in cocaine-taking behavior
Psychopharmacology (Berl)
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