Dopamine D‐2 receptor mediation of response suppression learning of young rats

Abstract

In three experiments, the effects of augmenting or blocking dopamine (DA) D-2 receptor activity on the ontogeny of response suppression learning of preweanling rat pups were determined. In the initial experiment, rat pups were trained to traverse a straight alley for nipple attachment to an anesthetized dam. When footshock (0.2 mA, 0.5 sec) was made contingent on responding, younger (11- and 13-day-olds) rat pups were deficient to older (17- and 19-day-olds) pups at withholding punished responding. In the subsequent experiments, response suppression learning was assessed after injecting 11- and 17-day-old rat pups with the specific DA D-2 agonist, LY 171555 (0.005-, 0.01-, and 0.1-mg/kg, i.p.), or the specific DA D-2 antagonist, sulpiride (5.0-, 15.0-, and 50.0-mg/kg, i.p.). LY 171555 enhanced the punished responding of both the 11- and 17-day-old rat pups; whereas, sulpiride increased the punished responding of the 17-, but not the 11-day-olds. In four additional experiments, the effects of LY 171555 and sulpiride on the locomotor activity, nociception, and reinforcement processes of 17-day-old rat pups was assessed. Rat pups given LY 171555 (0.01 mg/kg, i.p.) exhibited enhanced locomotor activity and a trend towards hyperanalgesia using a hot plate task. Sulpiride (15.0 mg/kg, i.p.) completely antagonized LY 171555's activity enhancing effects and had hyperalgesic properties. In two experiments, sulpiride did not affect the nonpunished appetitive responding of the 17-day-olds; whereas, haloperidol-treated pups responded on fewer reinforced trials than did saline-treated pups. Therefore, these results indicate that the response suppression learning of 17-day-old rat pups is mediated, at least partially, by a DAD-2 receptor system, and that D-2 receptors are also involved in the locomotor activity and nociceptive responses of young rat pups.

Dopaminergic modulation of kappa opioid-mediated ultrasonic vocalization, antinociception, and locomotor activity in the preweanling rat.

“…When given alone, NPA and cocaine did not alter tail-flick latencies, suggesting that DA receptor stimulation produces minimal analgesia in preweanling rats. Past research is consistent with this conclusion, because 17-day-old rats given quinpirole (a D 2 -like agonist) exhibited only a nonsignificant increase in paw-lick latencies using the hot plate test (McDougall & Nonneman, 1989). Even so, NPA potentiated the U-50,488-induced tail-flick latencies of 17-day-old rats (see Figure 2), indicating that DA systems are capable of modulating kappa-mediated antinociception during the preweanling period.…”

“…For example, using tail-flick, pressure, and irritant tests, both preweanling and adult rats exhibit pronounced analgesia after systemic administration of U-50,488 and other kappa opioid agonists (Barr, Miya, & Paredes, 1992; Giordano & Barr, 1987; Idänpään-Heikkilä, Kalso, & Seppälä, 1994; McLaughlin et al, 1995; VonVoigtlander, Lahti, & Ludens, 1983). It is uncertain whether DA agonists are capable of modulating U-50,488-induced antinociception (see Ushijima & Horita, 1993), although D 2 -like receptor agonists produce moderate analgesia in adult rats and mild analgesia in preweanling rats (Barasi & Duggal, 1985; McDougall & Nonneman, 1989; Suaudeau & Costentin, 1995). USV production is also affected by kappa opioid receptor stimulation, because preweanling rats emit substantial numbers of USVs after U-50,488 treatment (Barr, Wang, & Carden, 1994; Carden, Barr, & Hofer, 1991; Carden, Bortot, & Hofer, 1993; Kehoe & Boylan, 1994).…”

“…It was further hypothesized that direct and indirect DA agonists would attenuate U-50,488-induced USVs and augment U-50,488-induced antinociception in preweanling rats. The latter predictions were based on earlier studies in which DA agonists were administered in the absence of U-50,488 (see Barr & Wang, 1993; Kehoe & Boylan, 1992; McDougall & Nonneman, 1989).…”

Dopamine antagonists produce an age‐dependent increase in the responding of the young chick

“…As examples, sulpiride, a dopamine D, receptor antagonist, disrupts the response suppression performance of adult mice on a 1-trial passive avoidance task (Ichihara, Nabeshima, & Kameyama, 1988). Likewise, 17-day-old rat pups given sulpiride show increased punished responding when tested on a punished appetitive approach task; however, the response suppression responding of even younger rat pups (1 1-day-olds) is not affected by sulpiride treatment (McDougall & Nonneman, 1989). …”

Effects of SCH 23390 and sulpiride on the reinforced responding of the young rat.

“…Likewise, in adult rats, a similar dose of sulpiride is typically devoid of any behavioral effects; hence, it is possible that the 15.0 mg/kg dose of sulpiride was insufficient to affect the reinforced responding of the 17-day-old rat pups. However, this possibility seems unlikely because the enhanced locomotor activity of quinpirole-treated 17-day-old rat pups is fully antagonized by 15.0 mg/kg sulpiride (McDougall et al, 1990;McDougall & Nonneman, 1989). However, to more fully determine the effects of D2 receptor blockade on the approach responding of the young rat pup, various doses of sulpiride (5,0, 15.0, and 50.0 mg/kg) were given to 17-dayold rat pups, and latencies to traverse a straight alley for nipple attachment reward were recorded.…”