Opioid antagonists block the acquisition of ethanol-mediated conditioned tactile preference in infant rats - PubMed (original) (raw)

Opioid antagonists block the acquisition of ethanol-mediated conditioned tactile preference in infant rats

Michael Eduard Nizhnikov et al. Alcohol. 2009 Aug.

Abstract

It has been difficult to find conditioned preference for tactile cues paired with ethanol intoxication in rats. Toward understanding the ontogeny of ethanol reinforcement, we aimed at establishing a simple and reliable procedure for (1) assessing primary appetitive conditioning to ethanol in infant rats and (2) discerning the role the opioid system plays in ethanol-mediated conditioning at this age. Experiment 1 determined the parameters (i.e., dose, interval of conditioning) for assessing ethanol-mediated conditioning. Pups were then trained with differential Pavlovian conditioning (Experiments 2 and 3) in which ethanol intoxication (1.0-2.0 g/kg, intragastrically or intraperitoneally delivered) was paired with a tactile stimulus (sandpaper) while an alternative texture signaled the absence of ethanol's effects. Unpaired control conditions were also used. Tactile preferences were assessed after two conditioning sessions. Paired rats spent significantly more time on sandpaper than unpaired controls, an effect that was greater after intragastric administration of 1.0 than 2.0 g/kg ethanol. This effect was replicated in Experiments 4a and 4c and found to be inhibited by pretreatment with general (naloxone [NAL]) or specific (d-Pen-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 [CTOP] and naltrindole) opioid antagonists. Blood ethanol levels at conditioning were not altered by NAL (Experiment 4b). The study outlines a procedure that reveals appetitive conditioning to ethanol by infant rats. The results are discussed in terms of a potential ethanol-induced activation of the endogenous opioid system during the onset of the intoxication process.

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Figures

Figure 1

Blood ethanol content of subjects administered 1.0, or 2.0 g/kg ethanol (top and bottom panels, respectively) either i.p. or i.g. in Experiment 1. Blood ethanol concentration was measured at 5, 10, 20, 40, 80 and 120 minutes post administration. Each experimental group was composed by 6 animals.

Figure 2

Percent time spent on sandpaper (conditioned stimulus, CS+) as a function of conditioning procedures [sandpaper paired or unpaired with i.p or i.g. administration of ethanol (1.0 or 2.0 g/kg)]. Each of the eight groups had 9–12 animals. Asterisks indicate significant differences between a paired group and its corresponding unpaired control (p < 0.05). Vertical bars represent the standard error of the means (S.E.M.).

Figure 3

Percent time spent on sandpaper (conditioned stimulus, CS+) as a function of conditioning procedures. Subjects were exposed to a tactile cue (sandpaper CS+) either paired or unpaired with i.g. administration of 1.0 g/kg ethanol on 2 consecutive days. During conditioning, they were trained with a sequential CS−/CS+ differential conditioning procedure or with exposure to the CS+ only. Each of the four groups had 7–8 animals. Asterisks indicate significant differences between a paired group and its corresponding unpaired control (p < 0.05). Vertical bars represent the standard error of the means (S.E.M.).

Figure 4

Percent time spent on sandpaper (conditioned stimulus, CS+) as a function of conditioning procedures [sandpaper paired or unpaired with i.g. administration of 1.0 g/kg ethanol] and naloxone dose given prior to conditioning (0.0, 0.25, 0.75 or 1.5 mg/kg). Each group was composed by eight animals. Asterisks indicate significant differences between a paired group and its corresponding unpaired control (p < 0.05). Vertical bars represent the standard error of the means (S.E.M.).

Figure 5

Percent time spent on sandpaper (conditioned stimulus, CS+) as a function of conditioning procedures [sandpaper paired or unpaired with i.g. administration of 1.0 g/kg ethanol] and antagonist treatment prior to conditioning: animals could receive injections of CTOP (0.10 or 1.0 mg/kg), naltrindole (NALT, 1.0 or 5.0 mg/kg), or vehicle (0.0, vehicle). Groups were composed by 9 to 12 animals. Asterisks indicate significant differences between a paired group and its corresponding unpaired control (p < 0.05). Vertical bars represent the standard error of the means (S.E.M.).

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Opioid antagonists block the acquisition of ethanol-mediated conditioned tactile preference in infant rats - PubMed (original) (raw)