Dopamine Release in the Dorsal Striatum during Cocaine-Seeking Behavior under the Control of a Drug-Associated Cue

Abstract

Compulsive drug use is characterized by a pattern of drug seeking and consumption that becomes progressively habitual and less and less modifiable by external and internal factors. Although traditional views would posit that nigrostriatal dopamine (DA) neurons originating in the substantia nigra and innervating the dorsal striatum are primarily concerned with motor functions, recent studies have implicated the dorsal striatum in mediating stimulus-response (habit) learning. In this study, in vivo microdialysis in combination with a second-order schedule of cocaine reinforcement was used to investigate the role of the dorsal striatal dopamine innervation in well established drug-seeking behavior under the control of a drug-associated cue [light conditioned stimulus (CS+)]. Rats were initially trained to self-administer cocaine under a continuous reinforcement schedule where a response on one of two identical levers led to a 20 sec presentation of a light CS+ and an intravenous cocaine infusion (0.75 mg/kg). The response requirement for the CS+ and cocaine was then progressively increased until stable responding was established under a second-order schedule of reinforcement. During microdialysis, rats were presented with the cocaine-associated CS+ either noncontingently or contingent on responding during a session of cocaine-seeking behavior. The results showed a marked increase in DA release in the dorsal striatum during drug-seeking, when cocaine cues were presented contingently, but not when the same cue was presented noncontingently. These data indicate a possible involvement of the dopaminergic innervation of the dorsal striatum in well established, or habitual, cocaine-seeking behavior.

Nicotine-Associated Cues Maintain Nicotine-Seeking Behavior in Rats Several Weeks after Nicotine Withdrawal: Reversal by the Cannabinoid (CB1) Receptor Antagonist, Rimonabant (SR141716)

“…Recent studies have revealed that in the striatum, such mechanisms are strongly regulated by dopamine signaling and are also influenced by other signaling systems such as the endocannabinoid system. It is possible that nicotine-associated cues stimulate dopamine neurotransmission in specific brain regions as it was shown for cocaine-associated cues (Ito et al, 2000(Ito et al, , 2002Phillips et al, 2003). Rimonabant might prevent such activation and/ or its effects on postsynaptic transmission (Cohen et al, 2002).…”

The role of central dopamine D3 receptors in drug addiction: a review of pharmacological evidence

“…There is evidence suggesting that the nigrostriatal dopaminergic system plays an important role in habit formation, allowing animals to acquire and maintain performance [142]. Since, as previously mentioned, the nigrostriatal system is virtually devoid of D 3 receptors, it is possible that the inability of SB-277011-A to affect the self-administration of cocaine and nicotine is related to the relative lack of D 3 receptors in the nigrostriatal system.…”

Relapse to cocaine-seeking increases activity-regulated gene expression differentially in the striatum and cerebral cortex of rats following short or long periods of abstinence

“…This behavioral shift is accompanied and/or driven by a shift from prefrontal cortical to striatal control of behavior (Everitt and Wolf 2002;Ito et al 2002;Porrino et al 2004). The CPu becomes activated during cue-elicited cocaine craving in humans (Garavan et al 2000;Volkow et al 2006).…”

“…As associative learning becomes more habitual in nature, activity in the corticostriatal network shifts from a prefrontal cortical-dorsomedial striatal circuit to a sensorimotor cortical-dorsolateral striatal circuit (Jog et al 1999;Packard and Knowlton 2002;White and McDonald 2002;Balleine et al 2007). Since the process of addiction is thought to reflect the progressive development of compulsive behavior and/or loss of inhibitory control over impulsive behavior (Tiffany 1990;Jentsch and Taylor 1999;Everitt et al 2001;Vanderschuren and Everitt 2004), the role of the striatum, particularly the dorsolateral caudate-putamen (dlCPu), in the compulsive aspects of addiction has become a major focus of study (Everitt and Wolf 2002;Ito et al 2002;Everitt and Robbins 2005). Thus, extensive cocaine exposure may induce a transition from corticolimbic to corticostriatal control over decision-making and choice behavior as compulsive drug-seeking emerges Volkow et al 2006).…”