Time-Dependent Changes in Cocaine-Seeking Behavior and Extracellular Dopamine Levels in the Amygdala during Cocaine Withdrawal

Abstract

Cocaine and cocaine-associated cues elicit craving in addicts and reinstate cocaine-seeking behavior in rats. Craving and cocaine-seeking behavior may be mediated by withdrawalinduced changes in dopamine (DA) Cocaine-seeking behavior; Cocaine withdrawal; Dopamine; Amygdala; Reinstatement; Extinction; Self-administration Craving is thought to play a critical role in drug relapse (Dackis and Gold 1985;Gawin and Kleber 1986;Wallace 1989). Gawin and Kleber (1986) have suggested that early during withdrawal from a cocaine binge there is little or no craving, and that later during withdrawal there is intense craving that can be exacerbated by cocaine-paired cues. In the laboratory, addicts exposed to drug-related cues (Childress et al. 1988;Ehrman et al. 1992;Satel et al. 1995) or given a cocaine priming injection report intense craving (Jaffe et al. 1989;Kosten et al. 1992;Preston et al. 1993) and exhibit conditioned physiological changes (Ehrman et al. 1992). Similarly, animals with a history of cocaine self-administration exhibit reinstatement of extinguished cocaine-seeking behavior after presentation of cocaine-paired cues or a cocaine priming injection (Davis and Smith 1976;Stewart 1984;Stewart et al. 1984). In these studies, cocaine-seeking behavior is measured as nonreinforced lever-pressing behavior.Reinstatement of cocaine-seeking behavior may be mediated by enhanced dopamine (DA) neurotransmission because systemic administration of indirect (Gerber and Stretch 1975;de Wit and Stewart 1981;Worley et al. 1994) or direct DA receptor agonists (de Wit and Stewart 1981;Wise et al. 1990;Self et al. 1996) reinstates cocaine-seeking behavior. It has been suggested based on localization studies that the nucleus accumbens (NAc) is involved because drugs that enhance DA neu- Received September 11, 1997; revised November 7, 1997; accepted November 13, 1997. N EUROPSYCHOPHARMACOLOGY 1998 -VOL . 19 , NO . 1 Cocaine-Seeking Behavior and Dopamine 49 rotransmission in this region reinstate cocaine-seeking behavior (Stewart 1984). Studies have also examined conditioned DA neurotransmission in the NAc after presentation of cocaine-paired cues, but the results have been controversial. After presentation of a light paired previously with cocaine self-administration, in vivo voltammetry studies have demonstrated that putative DA-related signals increase in the NAc (Gratton and Wise 1994;Kiyatkin and Stein 1994;Kiyatkin 1995), whereas an in vivo microdialysis study indicated no changes in extracellular DA levels (Neisewander et al. 1996). Electrophysiological studies have demonstrated a change in neuronal firing in the NAc prior to cocainereinforced lever pressing (Chang et al. 1994; Deadwyler 1994, 1996; Peoples and West 1996). This anticipatory response may be DA mediated in some (Carelli and Deadwyler 1996), but not all cells (Chang et al. 1994). Furthermore, Fontana et al. (1993) found a context-dependent sensitization of both locomotor behavior and extracellular DA levels in the NAc after a cocaine challenge ...

Alcohol Relapse Induced by Discrete Cues Activates Components of AP-1 Transcription Factor and ERK Pathway in the Rat Basolateral and Central Amygdala

“…In line with clinical data, ethanol is a strong reinforcer for laboratory animals (Samson et al, 2000), and alcohol-associated cues elicit drug-seeking behavior in animals trained to self-administer alcohol, even after protracted abstinence (Shalev et al, 2002;Wedzony et al, 2003;Bienkowski et al, 2004). It has been postulated that both gene expression and protein synthesis are responsible for the persistent nature of addiction and the occurrence of relapse (Tran-Nguyen et al, 1998;Berke and Hyman, 2000;Shaham et al, 2000). Thus, the identification of brain circuits and molecular processes associated with cue-induced relapse to drug-seeking behavior seems to be crucial for understanding addiction processes (Asan, 1998;Shaham et al, 2003).…”

“…It is also worthy to note that dopaminergic fibers are more numerous in the BLA and CeA as compared to the MePD and BMP (Asan, 1998). This could make the former nuclei more sensitive to dopamine released upon stimulation with drug-and alcohol-related context or discrete stimuli (Tran-Nguyen et al, 1998).…”

Addiction-Related Alterations in D1 and D2 Dopamine Receptor Behavioral Responses Following Chronic Cocaine Self-Administration

“…Our results suggest that such changes, whether due to higher cocaine exposure or an inherent disposition, could result in enhancing D 2 and reducing D 1 receptor responsiveness, respectively. Furthermore, the emergence of these features from early to late withdrawal parallels time-dependent increases in cocaineseeking behaviors that have been shown to persist from weeks to months following chronic cocaine self-administration (Tran-Nguyen et al, 1998;Grimm et al, 2001). The further intensification of increased D 2 receptor function is particularly troublesome, since it could exacerbate the behavioral response to conditioned stimuli (cues) and stressful situations that activate dopamine release in rats and humans (Rouge-Pont et al, 1998;Phillips et al, 2003;Pruessner et al, 2004), and, thus, facilitate relapse to cocaine use despite efforts to abstain.…”

“…Moreover, higher preferred levels of cocaine intake in addicted animals could reflect a compensatory response to reduced D 1 receptor function. Furthermore, such differences could emerge or be exacerbated during withdrawal from cocaine, since the propensity for cocaine seeking increases in a timedependent manner from early to late withdrawal times (Tran-Nguyen et al, 1998;Grimm et al, 2001).…”

The Role of the Dorsomedial Prefrontal Cortex, Basolateral Amygdala, and Dorsal Hippocampus in Contextual Reinstatement of Cocaine Seeking in Rats

“…Second, contexts and explicit CSs were administered using different modes of stimulus presentation. Contexts were presented independent of responding, whereas explicit CSs had to be presented response-contingently because passive presentation of these stimuli results in little or no cocaine-seeking behavior (Tran-Nguyen et al, 1998;. These differences in stimulus presentation are important because they likely determine the relationship of these stimuli to the US.…”