Impact of Repeated Intravenous Cocaine Administration on Incentive Motivation Depends on Mode of Drug Delivery.

Impact of repeated intravenous cocaine administration on incentive motivation depends on mode of drug delivery.

Addict Biol. 2013 May 3;
Leblanc KH, Maidment NT, Ostlund SB

The incentive sensitization theory of addiction posits that repeated exposure to drugs of abuse, like cocaine, can lead to long-term adaptations in the neural circuits that support motivated behavior, providing an account of pathological drug-seeking behavior. Although pre-clinical findings provide strong support for this theory, much remains unknown about the conditions that support incentive sensitization. The current study examined whether the mode of cocaine administration is an important factor governing that drug’s long-term impact on behavior. Separate groups of rats were allowed either to self-administer intravenous cocaine or were given an equivalent number and distribution of unsignaled cocaine or saline infusions. During the subsequent test of incentive motivation (Pavlovian-to-instrumental transfer), we found that rats with a history of cocaine self-administration showed strong cue-evoked food seeking, in contrast to rats given unsignaled cocaine or saline. This finding indicates that the manner in which cocaine is administered can determine its lasting behavioral effects, suggesting that subjective experiences during drug use play a critical role in the addiction process. Our findings may therefore have important implications for the study and treatment of compulsive drug seeking. HubMed – addiction

Neuropeptide Y Y2 R blockade in the central amygdala reduces anxiety-like behavior but not alcohol drinking in alcohol-dependent rats.

Addict Biol. 2013 May 3;
Kallupi M, Vendruscolo LF, Carmichael CY, George O, Koob GF, Gilpin NW

Electrophysiological data suggest a dual role of Y2 receptors (Y2 Rs) as autoreceptors regulating neuropeptide Y release and heteroceptors regulating gamma-aminobutyric acid release in the central amygdala (CeA). Here, we report that neither systemic (JNJ-31020028) nor intra-CeA (BIIE0246) Y2 R antagonism altered operant alcohol responding by alcohol-dependent or non-dependent rats. Conversely, BIIE0246 in the CeA reduced anxiety-like behavior in alcohol-dependent and alcohol-naïve rats. The finding that Y2 R antagonism reduces anxiety-like behavior but not alcohol drinking suggests that these two effects may occur via different functions of the Y2 R (e.g. autoreceptor versus heteroceptor function). HubMed – addiction

Functional interaction between presynaptic ?6?2-containing nicotinic and adenosine A2A receptors in the control of dopamine release in the rat striatum.

Br J Pharmacol. 2013 May 3;
Garção P, Szabó EC, Wopereis S, Castro AA, Tomé AR, Prediger RD, Cunha RA, Agostinho P, Köfalvi A

BACKGROUND AND PURPOSE: Presynaptic nicotinic acetylcholine receptors (nAChRs) and adenosine A2A receptors (A2A Rs) are involved in the control of dopamine release and are putative therapeutic targets in Parkinson’s disease and addiction. Since A2A Rs have been reported to interact with nAChRs, here we aimed at mapping the possible functional interaction between A2A Rs and nAChRs in rat striatal dopaminergic terminals. EXPERIMENTAL APPROACH: We pharmacologically characterized the release of dopamine and defined the localization of nAChR subunits in rat striatal nerve terminals in vitro, and carried out locomotor behavioral sensitization in rats in vivo. KEY RESULTS: In striatal nerve terminals, the selective A2A R agonist CGS21680 (30 nM) inhibited, while the A2A R antagonist ZM241385 potentiated the nicotine-stimulated [(3) H]dopamine release. Upon blockade of the ?6 subunit-containing nAChRs, the remaining nicotine-stimulated [(3) H]dopamine release was no longer modulated by A2A R ligands. In the locomotor sensitization experiments, nicotine enhanced the locomotor activity on day 7 of repeated nicotine injection, an effect which no longer persisted after one week of drug withdrawal. Notably, ZM241385-injected rats developed locomotor sensitization to nicotine already on day 2, which remained persistent upon nicotine withdrawal. CONCLUSIONS AND IMPLICATIONS: These results provide the first evidence for a functional interaction between nicotinic and adenosine A2A receptors in striatal dopaminergic terminals, with likely therapeutic consequences for smoking, Parkinson’s disease and other dopaminergic disorders. HubMed – addiction