Music and methamphetamine: conditioned cue-induced increases in locomotor activity and dopamine release in rats

Abstract

Associations between drugs of abuse and cues facilitate the acquisition and maintenance of addictive behaviors. Although significant research has been done to elucidate the role that simple discriminative or discrete conditioned stimuli (e.g., a tone or a light) play in addiction, less is known about complex environmental cues. The purpose of the present study was to examine the role of a musical conditioned stimulus by assessing locomotor activity and in vivo microdialysis. Two groups of rats were given non-contingent injections of methamphetamine (1.0 mg/kg) or vehicle and placed in standard conditioning chambers. During these conditioning sessions both groups were exposed to a continuous conditioned stimulus, in the form of a musical selection ("Four" by Miles Davis) played repeatedly for 90 min. After seven consecutive conditioning days subjects were given one day of rest, and subsequently tested for locomotor activity or dopamine release in the absence of drugs while the musical conditioned stimulus was continually present. The brain regions examined included the basolateral amygdala, nucleus accumbens, and prefrontal cortex. The results show that music is an effective contextual conditioned stimulus, significantly increasing locomotor activity after repeated association with methamphetamine. Furthermore, this musical conditioned stimulus significantly increased extracellular dopamine levels in the basolateral amygdala and nucleus accumbens. These findings support other evidence showing the importance of these brain regions in conditioned learning paradigms, and demonstrate that music is an effective conditioned stimulus warranting further investigation.

Figure 1

Diagrammatic representation of time course for classical conditioning and activity/microdialysis tests.

Figure 2

Representative probe placements for A) basolateral amygdala, B) nucleus accumbens, and C) medial prefrontal cortex.

Figure 2

Representative probe placements for A) basolateral amygdala, B) nucleus accumbens, and C) medial prefrontal cortex.

Figure 2

Representative probe placements for A) basolateral amygdala, B) nucleus accumbens, and C) medial prefrontal cortex.

Figure 3

Effects of a conditioned musical cue on locomotor activity. Data points represent mean summed locomotor activity for the 90 min test session (± SEM). Refer to Table 1 for a detailed depiction of the conditioning and test conditions for each group. A) Meth-Music test group and the three METH control groups. * p<0.05 B) Meth-Music test group and the four saline control groups. * p<0.05

Figure 3

Effects of a conditioned musical cue on locomotor activity. Data points represent mean summed locomotor activity for the 90 min test session (± SEM). Refer to Table 1 for a detailed depiction of the conditioning and test conditions for each group. A) Meth-Music test group and the three METH control groups. * p<0.05 B) Meth-Music test group and the four saline control groups. * p<0.05

Figure 4

Effects of conditioned musical cue in the basolateral amygdala. Time course of extracellular dopamine (mean ± SEM) during microdialysis testing. Musical cue presentation was initiated immediately prior to collection of sample 7 and terminated immediately following collection of sample 11. * p<0.05

Figure 5

Effects of conditioned musical cue in the nucleus accumbens. Time course of extracellular dopamine (mean ± SEM) during microdialysis testing. Musical cue presentation was initiated immediately prior to collection of sample 7 and terminated immediately following collection of sample 11. * p<0.05

Figure 6

Effects of conditioned musical cue in the medial prefrontal cortex. Time course of extracellular dopamine (mean ± SEM) during microdialysis testing. Musical cue presentation was initiated immediately prior to collection of sample 7 and terminated immediately following collection of sample 11.