TY - JOUR
T1 - Discriminative stimulus properties of cocaine
T2 - modulation by dopamine D1 receptors in the nucleus accumbens
AU - Callahan, Patrick M.
AU - De La Garza, Richard
AU - Cunningham, Kathryn A.
PY - 1994/6
Y1 - 1994/6
N2 - Dopamine (DA) D1 and D2 receptors are involved in mediating the behavioral effects of cocaine, including its discriminative stimulus properties. The purpose of the present study was to investigate the role of the nucleus accumbens and, in particular, accum bens DA D1 receptors in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IP) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution tests, systemic (IP) administration of cocaine (0.625-20 mg/kg) produced a dose-related increase in cocaine-appropriate responding. Microinjections of cocaine (2.5-40 μg) into the nucleus accumbens also engendered dose-dependent and complete substitutions (> 80% drug-lever responding) for the systemic training dose of cocaine, whereas intra-accumbens artificial cerebrospinal fluid (1 μl/side) produced primarily saline-appropriate responding. In antagonism tests, pretreatment with the DA D1 antagonist SCH 23390 (3-12 μg/kg) completely antagonized (<20% drug-lever responding) a dose of cocaine (5 mg/kg) that produced greater than 90% cocaine-lever responding when given alone. Additionally, intra-accumbens injections of SCH 23390 (0.025-0.4 μg) prior to systemic cocaine (5 mg/kg) also significantly blocked the cocaine stimulus. The present results confirm the importance of the nucleus accumbens in mediating the discriminative stimulus properties of cocaine and suggest a primary role of accumbens DA D1 receptors in modulating this behavior.
AB - Dopamine (DA) D1 and D2 receptors are involved in mediating the behavioral effects of cocaine, including its discriminative stimulus properties. The purpose of the present study was to investigate the role of the nucleus accumbens and, in particular, accum bens DA D1 receptors in modulating the stimulus effects of cocaine. Thus, rats were trained to discriminate cocaine (10 mg/kg, IP) from saline using a two-lever, water-reinforced FR 20 drug discrimination task. In substitution tests, systemic (IP) administration of cocaine (0.625-20 mg/kg) produced a dose-related increase in cocaine-appropriate responding. Microinjections of cocaine (2.5-40 μg) into the nucleus accumbens also engendered dose-dependent and complete substitutions (> 80% drug-lever responding) for the systemic training dose of cocaine, whereas intra-accumbens artificial cerebrospinal fluid (1 μl/side) produced primarily saline-appropriate responding. In antagonism tests, pretreatment with the DA D1 antagonist SCH 23390 (3-12 μg/kg) completely antagonized (<20% drug-lever responding) a dose of cocaine (5 mg/kg) that produced greater than 90% cocaine-lever responding when given alone. Additionally, intra-accumbens injections of SCH 23390 (0.025-0.4 μg) prior to systemic cocaine (5 mg/kg) also significantly blocked the cocaine stimulus. The present results confirm the importance of the nucleus accumbens in mediating the discriminative stimulus properties of cocaine and suggest a primary role of accumbens DA D1 receptors in modulating this behavior.
KW - Cocaine
KW - Dopamine D and D receptors
KW - Drug discrimination
KW - Microinjection
KW - Nucleus accumbens
KW - Rat
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U2 - 10.1007/BF02244759
DO - 10.1007/BF02244759
M3 - Article
C2 - 7862881
AN - SCOPUS:0028246317
SN - 0033-3158
VL - 115
SP - 110
EP - 114
JO - Psychopharmacology
JF - Psychopharmacology
IS - 1-2
ER -