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Basal forebrain cholinergic lesions attenuate the reinstatement of cocaine-seeking produced by a discriminative stimulus in goal-trackers but not sign-trackers

Jones JL, Pitchers KK, Robinson TE, Sarter M (2015) Basal forebrain cholinergic lesions attenuate the reinstatement of cocaine-seeking produced by a discriminative stimulus in goal-trackers but not sign-trackers. Neuroscience 2015 Abstracts 411.15/L-15. Society for Neuroscience, Chicago IL.

Summary: Goal-trackers (GTs), compared to sign-trackers (STs), express higher levels of acetylcholine when performing a cue detection and processing task. We hypothesized, therefore, that GTs utilize their basal forebrain cholinergic systems differently and to a greater extent than STs, such that this system may be critical for signal-induced behavior in GTs but not STs. The purpose of this experiment was to investigate individual variation in the reinstatement of drug-seeking behavior produced by a signal indicating cocaine availability (a discriminative stimulus), as well as the influence of the basal forebrain cholinergic system. STs and GTs were trained to self-administer cocaine using an intermittent access (IntA) procedure. The IntA procedure involved allowing animals access to cocaine for discrete 5-min drug available periods indicated by a light signal (DS+) separated by 25-min no drug available periods indicated by a different signal (DS-) in a different location than the DS+. This procedure results in ‘spiking’ brain levels of cocaine. Once stable performance was achieved on this procedure, animals underwent extinction training where the context remained similar to the IntA procedure but was now devoid of both DSs and an active response no longer had any consequence. STs and GTs did not differ in the acquisition or expression of self-administration or extinction training. After behavior was stably extinguished, half of the subjects received bilateral infusions of the cholinotoxic immunotoxin 192 IgG-saporin into the basal forebrain, while the other half received sham surgeries. Animals underwent 5 days of re-extinction. Finally, they underwent a reinstatement test during which the DS+ was presented non-contingently for 2 sec on a variable time schedule. Current results show that the ST-lesion group and both sham groups reinstated responding upon exposure to the DS+, compared to the last day of extinction. In contrast, the GT-lesion group did not reinstate responding, relative to the last day of extinction and, additionally, showed fewer active responses during the reinstatement test than the GT-sham group. Our findings suggest that the basal forebrain cholinergic system is involved in the reinstatement of drug-seeking behavior produced by a signal indicating drug availability in some animals (GTs), but not others (STs), further supporting the notion that drug cues are processed very differently in STs and GTs.

Related Products: 192-IgG-SAP (Cat. #IT-01)