lever presses were not reinforced.  At the start of each session, rats received two priming injections to signal the availability of drug.  The syringe pump system, cue light, and tone were controlled by an IBM PC computer via a LabLinc I/O panel.  The computer recorded both reinforced and non-reinforced lever presses.

Rats were allowed to self-administer cocaine (750 g/kg/inj) until their response rates stabilized (10% for two consecutive days). On subsequent test days, rats were allowed to self-administer SKF82958 (3, 10, or 30 g/kg/inj) alone or in combination with either SCH23390 (0.1, 0.3, 1, 3, or 10 g/kg/inj) or eticlopride (0.3, 1, 3, or 10 g/kg/inj). Drug combinations and doses were randomly assigned. All drugs were dissolved in bacteriostatic 0.9% NaCl solution, and drug solutions were sterile filtered (0.2 m Acrodisc). The volume of saline vehicle added was calculated based on the rat's weight, measured 45 min before each session. Cocaine was provided by the National Institute of Drug Abuse. SKF82958 [()-6-chloro-7,8-dihydroxy-3-allyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrobromide], SCH23390 [R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl- 2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride], and eticlopride [S(-)-3-chloro-5-ethyl-N-[(1-ethyl-2-pyrrolidinyl)methyl]-6-hydroxy-2-methoxy-benzamide hydrochloride] were obtained from Research Biochemicals Incorporated.

Statistical computations were performed using Systat 6.0. Response rates at each dose of SKF82958, alone versus in combination with each antagonist, were analyzed using a one-way ANOVA and posthoc tests with Bonferroni adjustments.

Results

Figure 1 shows the effects of SCH23390 dose on self-administration of each dose of SKF82958. When combined with the low dose of SKF82958 (3 g/kg/inj), the lowest dose of SCH23390 (0.1 g/kg/inj) caused a small increase in response rate. Further increases in the SCH23390 dose (0.3, 1, 3 g/kg/inj) produced significant decreases in self-administration of SKF82958 3 g/kg/inj. SCH23390 exerted similar, but more pronounced, effects on self-administration of the higher SKF82958 doses (10 and 30 g/kg/inj). Responses for SKF82958 10 g/kg/inj initially increased with increasing SCH23390 dose (0.1 and 0.3 g/kg/inj) before rapidly declining at the higher antagonist doses, starting at 1 g/kg/inj.

    

Similarly, responses for SKF82958 30 g/kg/inj increased significantly with increasing antagonist doses and declined at SCH23390 3 g/kg/inj.

Figure1.gif (6723 bytes)
Figure 1
Effect of SCH23390 (0.1, 0.3, 1, 3, 10 u
g/kg/inj) on self-administration of SKF82958 (3, 10, 30 ug/kg/inj ).  Data are presented as mean total self-injections during 3 hr sessions.  *p<0.05 versus same dose of SKF82958 alone.

The effect of eticlopride dose on self-administration of each dose of SKF82958 is shown in Figure 2. Self-administration of SKF82958 3 g/kg/inj decreased with increasing eticlopride dose to significantly lower levels than baseline.  When combined with the intermediate SKF82958 dose (10 g/kg/inj), lower doses of eticlopride (0.3 and 1 g/kg/inj) did not affect response rate.  Self-administration began to decrease at 3 g/kg/inj of eticlopride, and the decline paralleled that seen in self-administration of 3 g/kg/inj SKF82958 in combination with similar eticlopride doses.   Self-administration of 30 g/kg/inj SKF82958 was unaffected by the lower eticlopride doses (0.3 and 1 g/kg/inj).  Responses were decreased by eticlopride 3 g/kg/inj and remained unchanged when the antagonist dose was increased further.   However, unlike the fall in response rates for

Figure2.gif (6078 bytes)
Figure 2
Effect of eticlopride (0.3, 1, 3, 10
ug/kg/inj).  Data are presented as mean total self-injection during 3 h sessions.  *p<0.05 versus same dose of SKF82958 alone, **p<0.01 versus same dose of SKF82958 alone.

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Mohammad Helmy - Effects of the D1-Antagonist SCH23390... [1] [2] [3] [4] [5] [6]