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Comparative Study
. 2005 Sep 21;25(38):8665-70.
doi: 10.1523/JNEUROSCI.0925-05.2005.

Involvement of the dorsal striatum in cue-controlled cocaine seeking

Louk J M J Vanderschuren  1 , Patricia Di Ciano, Barry J Everitt
Affiliations
Comparative Study

Involvement of the dorsal striatum in cue-controlled cocaine seeking

Louk J M J Vanderschuren et al. J Neurosci. .

Abstract

Through association with the interoceptive effects of drugs of abuse, neutral environmental stimuli can gain motivational properties themselves, becoming conditioned reinforcers that can evoke craving and relapse to drug seeking. Nucleus accumbens dopamine (DA) neurotransmission plays an important role in the reinforcing effect of cocaine itself, but, unlike nucleus accumbens glutamate, it seems not to mediate the conditioned reinforcing properties of cocaine-paired stimuli. Dorsal striatal DA transmission, in contrast, has been shown to be enhanced during cocaine seeking under a second-order schedule of reinforcement, which depends on the conditioned reinforcing properties of cocaine-associated stimuli. Therefore, the aim of the present study was to evaluate the role of DA and glutamate transmission in the dorsal striatum in cue-controlled cocaine seeking. Infusion of the DA receptor antagonist alpha-flupenthixol into the dorsal striatum decreased cocaine seeking under a second-order schedule of reinforcement. In addition, intradorsal striatal infusion of the AMPA/kainate (KA) receptor antagonist LY293558 (3SR, 4aRS, 6RS, 8aRS-6-[2-(iH-tetrazol-5-yl)ethyl]-1,2,3,4,4a,5,6,7,8,8a-decahydroiso-quinoline-3-carboxylic acid), but not the NMDA receptor antagonist AP-5, also decreased cue-controlled cocaine seeking. These data show that stimulation of DA and AMPA/KA receptors in the dorsal striatum is critical for well established drug seeking that depends on the reinforcing effects of cocaine-associated stimuli. In addition, given the importance of the dorsal striatum in stimulus-response habit learning, these data suggest that the habitual or compulsive quality of persistent drug seeking depends on dorsal striatal mechanisms.

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Figures

Figure 1.
Figure 1.
Location of the tips of injection cannulas within the dorsal striatum (filled circles; n = 13). Distances are in millimeters from bregma (adapted from Paxinos and Watson, 1986). AP, Anteroposterior.
Figure 2.
Figure 2.
Effects of the DA receptor antagonist α-flupenthixol on self-administration of cocaine under a second-order schedule of reinforcement. Left, α-Flupenthixol infusion into the dorsal striatum decreased the number of active responses in the first, drug-free interval. Right, After infusion in the dorsal striatum, α-flupenthixol did not influence inactive lever presses. Data are presented as mean ± SEM responses during the first 15 min interval of the session. *p < 0.05, different from vehicle (Student–Newman–Keuls test).
Figure 3.
Figure 3.
Effects of the AMPA/KA receptor antagonist LY293558 on self-administration of cocaine under a second-order schedule of reinforcement. Left, LY293558 infusion into the dorsal striatum decreased the number of active lever presses in the first, drug-free interval. Right, LY293558 into the dorsal striatum did not affect the number of inactive responses. Data are presented as mean ± SEM responses during the first 15 min interval of the session. *p < 0.05, different from vehicle (Student–Newman–Keuls test).
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References

    1. Bradberry CW, Barrett-Larimore RL, Jatlow P, Rubino SR (2000) Impact of self-administered cocaine and cocaine cues on extracellular dopamine in mesolimbic and sensorimotor striatum in rhesus monkeys. J Neurosci 20: 3874–3883. - PMC - PubMed
    1. Brown EE, Fibiger HC (1992) Cocaine-induced conditioned locomotion: absence of associated increases in dopamine release. Neuroscience 48: 621–629. - PubMed
    1. Caine SB, Lintz R, Koob GF (1992) Intravenous self-administration techniques in animals. In: Behavioral neuroscience: a practical approach (Sahgal A, ed), pp 117–143. Oxford: Oxford UP.
    1. Caine SB, Heinrichs SC, Coffin VL, Koob GF (1995) Effects of the dopamine D-1 antagonist SCH 23390 microinjected into the accumbens, amygdala or striatum on cocaine self-administration in the rat. Brain Res 692: 47–56. - PubMed
    1. Cardinal RN, Aitken MRF (2001) Whisker, version 2.2, computer software, http://www.whiskercontrol.com.

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