Involvement of the olfactory tubercle in cocaine reward: intracranial self-administration studies - PubMed (original) (raw)

Involvement of the olfactory tubercle in cocaine reward: intracranial self-administration studies

Satoshi Ikemoto. J Neurosci. 2003.

Abstract

Cocaine has multiple actions and multiple sites of action in the brain. Evidence from pharmacological studies indicates that it is the ability of cocaine to block dopamine uptake and elevate extracellular dopamine concentrations, and thus increase dopaminergic receptor activation, that makes cocaine rewarding. Lesion studies have implicated the nucleus accumbens (the dorsal portion of the "ventral striatum") as the probable site of the rewarding action of the drug. However, the drug is only marginally self-administered into this site. We now report that cocaine (60 or 200 mm in 75 nl/infusion) is readily self-administered into the olfactory tubercle, the most ventral portion of the ventral striatum. Cocaine (200 mm) was self-administered marginally into the accumbens shell but not into the core, dorsal striatum, or ventral pallidum. In addition, cocaine injections (200 mm in 300 nl) into the tubercle but not the shell or ventral pallidum induced conditioned place preference. Rewarding effects of cocaine in the tubercle were blocked by coadministration of dopamine D1 or D2 antagonists (1 mm SCH 23390 or 3 mm raclopride) and were not mimicked by injections of the local anesthetic procaine (800 mm). In conclusion, the tubercle plays a critical role in mediating rewarding action of cocaine.

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Figures

Figure 1.

Figure 1.

Injection sites of cocaine administration. A, Coronal sections (Paxinos and Watson, 1997) show target sites with cannula insertion angles. B, Histological results of all rats except the dorsal striatum subjects (for behavioral data, see Fig. 2) are summarized on tyrosine hydroxylase-stained sections. Color codes of the dots are consistent with those of the regions in A. C, Cresyl violet-stained sections show representative injection sites for target sites. OT, Olfactory tubercle.

Figure 2.

Figure 2.

Intracranial self-administration of cocaine. A, Mean rates of cocaine self-administration are shown separately for the target sites [anteromedial olfactory tubercle (OT), n = 16; anterolateral OT, n = 6; posteromedial OT, n = 10; shell, n = 10; core, n = 13; pallidum, n = 7; dorsal striatum, n = 6]; Error bars indicate SEM. *Significant difference compared with respective vehicle sessions, p < 0.05. B, Event records show representative patterns of self-administration into the anteromedial tubercle. Each vertical line on the horizontal line indicates the time point of an infusion. The number at the right of the horizontal line indicates total infusions in that session.

Figure 3.

Figure 3.

Two-lever discrimination. Rats (n = 6) did not respond on the active lever more than the inactive lever when active lever presses were rewarded with vehicle (VEH) in session 1. When active lever presses were rewarded with cocaine (COC) in sessions 2-4, they increased responding and responded on the active lever significantly more than the inactive lever. Data are mean lever presses per session; error bars indicate SEM. *Significant difference compared with inactive lever counts, p < 0.01.

Figure 4.

Figure 4.

Conditioned place preference induced by cocaine injections (200 m

m

in 300 nl) into the anteromedial tubercle (n = 10) but not the shell (n = 10) or ventral (V.) pallidum (n = 11). Mean place preference scores (time spent in the drug-associated side - time spent in the vehicle-associated side) are shown; error bars indicate SEM. *Significant difference compared with baseline preference, p < 0.05.

Figure 5.

Figure 5.

Roles of local anesthesia and dopamine receptors in cocaine reward. A, Data (n = 6) are mean infusion rates; error bars indicate SEM. *Significant difference compared with respective cocaine session, p < 0.05. B, Event records show representative patterns of self-administration into the anteromedial tubercle. The local anesthetic procaine (800 m

m

; an concentration equipotent to 200 m

m

cocaine in blocking Na+ channels) did not sustain self-administration (A, B). Coadministration of the D1 antagonist SCH 23390 (SCH+COC) or the D2 antagonist raclopride (RACL+COC) did not sustain self-administration (A, B).

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