Dopamine D1 and D2 antagonist effects on response likelihood and duration

Abstract

Experimentally induced and parkinsonian disruptions in dopamine (DA) transmission are associated with motor abnormalities that include a reduced likelihood of behavioral response initiation and an increased duration of executed responses. Here we investigated the dopamine receptor subtypes involved in regulating these two aspects of behavior. We examined the effects of D1 family (D1/D5) antagonist R(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine hydrochloride (SCH23390; 0, 0.04, 0.08, or 0.16 mg/kg) and D2/D3 antagonist 3,5-dichloro-N-(1-ethylpyrrolidin-2-ylmethyl)-2-hydroxy-6-methoxybenzamide (+)-tartrate salt (raclopride; 0, 0.2, or 0.4 mg/kg) on the likelihood and duration of a cued Pavlovian approach and a cued operant lever-press response. While the high doses of the D1 and D2 antagonists produced similar levels of overall locomotor suppression, only the D2 antagonist increased the duration of time that animals' heads remained in the food compartment during both Pavlovian and operant task performance. In contrast, D1 antagonist SCH23390 decreased the proportion of trials in which animals executed both the Pavlovian approach and operant lever-press, while raclopride did not. The results suggest that D2 receptor blockade preferentially increases response duration, and, under the simple discrete-trial procedures employed here, D1 receptor blockade preferential reduces Pavlovian and operant response likelihood.

Figure 1

Raster plots of individual head entries (horizontal lines) over the 28 trials (rows from bottom to top of y-axis) of the test session for representative animals performing the cued approach task under the influence of vehicle (top), D1 antagonist SCH23390 (middle) or D2 antagonist raclopride (bottom). D1 receptor blockade reduced the likelihood of head entries to the food compartment without affecting the duration of individual head entries. In contrast, D2 receptor blockade had little effect on head entry likelihood, but increased the duration of individual head entries.

Figure 2

Probability of the animal's head being inside the food compartment (y-axis) for each successive 100 ms bin during the 16 s before CS onset (-16 to 0), and the 10 s after the 500 ms CS in the cued approach task. D1 antagonist SCH23390 (top) did not increase head entry duration, but reduced the proportion of trials for which the animal responded to the CS, as reflected in the lower peaks after CS presentation. D2 antagonist raclopride (bottom) increased the duration of individual head entries without impairing initiation to the CS.

Figure 3

Mean ± SEM proportion of the 28 Cued Approach trials missed (i.e., with response latency of > 10 s). D1 receptor blockade (left) significantly increased the proportion of trials for which animals failed to respond to the CS, while D2 receptor blockade (right) did not. Dunnett's comparison to vehicle control p<.001**

Figure 4

Mean ± SEM proportion of the 28 Cued Lever-press trials missed (i.e., with response latency of > 10 s). D1 receptor blockade (left) significantly increased the proportion of trials for which animals failed to respond to the cue, while D2 receptor blockade (right) did not. Dunnett's comparison to vehicle control, p<.01*; p<.001**

Figure 5

Locomotor counts for animals under the influence of 0, 0.04, 0.08, or 0.16 mg/kg of D1 antagonist SCH23390 (left) or 0, 0.2, or 0.4 mg/kg of D2 antagonist raclopride (right) assessed in rats performing the cued approach task. Dunnett's comparison to vehicle control, p<.05 *.