Experimental anxiety and the reinforcing effects of ethanol in rats

Blatt, Solange Lúcia; Takahashi, Reinaldo Ν.

doi:10.1590/s0100-879x1999000400013

Cited by 24 publications

(7 citation statements)

References 22 publications

(23 reference statements)

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“…Our lack of preference behavior is in line with previous reports in adult male rats (Blatt and Takahashi 1999; Jones et al 2009). Although CPP may be difficult to establish with ethanol in naive rats, previous studies have shown that pre-treatment with ethanol before conditioning facilitates this effect in male rats (Beinkowski et al 1996; Biala and Kotlinska 1998; Ciccocioppo et al 1999; Gauvin and Holloway 1991; Maldonado-Devincci et al 2010; Quintanilla and Tampier 2011) and mice (Nocjar et al 1999).…”

Section: Discussionsupporting

confidence: 93%

Female Rats Display Enhanced Rewarding Effects of Ethanol That Are Hormone Dependent

Torres

Walker

Beas

et al. 2013

Alcohol Clin Exp Res

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Background Ethanol abuse is a major health and economic concern, particularly for females who appear to be more sensitive to the rewarding effects of ethanol. This study compared sex differences to the rewarding and aversive effects of ethanol using place-conditioning procedures in rats. Methods Separate groups of adult (male, female, ovariectomized [OVX] female) and adolescent (male and female) rats received ethanol (0, 0.5, 1.0, 2.0 or 2.5 g/kg; ip) and were confined to their initially non-preferred side of our conditioning apparatus for 30 minutes. On alternate days, they received saline and were confined to the other side. Following 5 drug pairings, the rats were re-tested for preference behavior. Separate cohorts of the same groups of rats were injected with a similar dose range of ethanol and blood ethanol levels (BELs) were compared 30 minutes later. Results Ethanol produced rewarding or aversive effects in a dose-dependent manner. An intermediate dose of ethanol (1.0 g/kg) produced rewarding effects in adult female but not male or OVX female rats, suggesting that ovarian hormones facilitate the rewarding effects of ethanol. Similarly, this intermediate dose of ethanol produced rewarding effects in adolescent female but not male rats. The highest dose of ethanol (2.5 g/kg) produced aversive effects that were similar across all adult groups. However, the aversive effects of ethanol were lower in adolescents than adults, suggesting that adolescents are less sensitive to the aversive effects of ethanol. The aversive effects of ethanol did not vary across the estrous cycle in intact adult females. There were also no group differences in BELs, suggesting that our results are not related to ethanol metabolism. Conclusion Our results in rats suggest that human females may be more vulnerable to ethanol abuse due to enhanced rewarding effects of this drug that are mediated by the presence of ovarian hormones.

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Section: Discussionsupporting

confidence: 93%

Female Rats Display Enhanced Rewarding Effects of Ethanol That Are Hormone Dependent

Torres

Walker

Beas

et al. 2013

Alcohol Clin Exp Res

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“…Spanagel et al (3) reported that anxiety levels were positively correlated with alcohol consumption in Wistar rats selected from a heterogeneous group for individual differences in anxietyrelated behavior on the elevated plus maze, suggesting a link between emotionality and alcohol consumption. This was confirmed in our laboratory using the conditioned place preference paradigm (4), since a significant place preference for the ethanol-paired compartment was shown by rats previously selected for anxiety. Also, in this context Möller et al (5) showed that bilateral lesions of the central amygdala, an important region for anxiety-related behavior (6), reduced both experimental anxiety and voluntary ethanol intake.…”

Section: Introductionsupporting

confidence: 59%

Comparison of voluntary ethanol intake by two pairs of rat lines used as genetic models of anxiety

Silva¹,

Ramos

Takahashi

2004

Braz J Med Biol Res

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The relationship between anxiety-related behaviors and voluntary ethanol intake was examined in two pairs of rat lines by the oral ethanol self-administration procedure. Floripa high (H) and low (L) rats selectively bred for contrasting anxiety responses in the open-field test, and two inbred strains, spontaneously hypertensive rats (SHR) and Lewis rats which are known to differ significantly when submitted to several behavioral tests of anxiety/emotionality, were used (9-10 animals/line/sex). No differences in the choice of ethanol solutions (2%, days 1-4, and 4%, days 5-8, respectively) in a 2-bottle paradigm were detected between Floripa H and L rats (1.94 ± 0.37 vs 1.61 ± 0.37 g/kg for ethanol intake on day 8 by the Floripa H and L rat lines, respectively). Contrary to expectations, the less anxious SHR rats consumed significantly more ethanol than Lewis rats (respective intake of 2.30 ± 0.45 and 0.72 ± 0.33 g/kg on day 8) which are known to be both addiction-prone and highly anxious. Regardless of strain, female rats consumed more ethanol than males (approximately 46%). The results showed no relationship between high anxiety and voluntary intake of ethanol for Floripa H and L rats. A negative association between these two variables, however, was found for SHR and Lewis rat strains. Data from the literature regarding the association between anxiety and alcohol intake in animal models are not conclusive, but the present results indicate that factors other than increased inborn anxiety probably lead to the individual differences in ethanol drinking behavior.

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“…The relationship between anxiety and ethanol has been a matter of considerable controversy. It has been demonstrated that a significant ethanol-CPP in rats previously selected to be anxious in the elevated plus maze, but not in the 'nonanxious rats' (Blatt and Takahashi, 1999). Spanagel et al (1995), showed a significantly higher intake and preference for ethanol in rats selected as anxious in the plus maze test, which led them to suggest that the degree of anxiety may underlie, at least in part, the initial motivation to drink alcohol.…”

Section: Discussionmentioning

confidence: 99%

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

Houchi

Babovic

Pierrefiche

et al. 2004

Neuropsychopharmacol

172

144

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Cannabinoids and ethanol activate the same reward pathways, and recent advances in the understanding of the neurobiological basis of alcoholism suggest that the CB 1 receptor system may play a key role in the reinforcing effects of ethanol and in modulating ethanol intake. In the present study, male CB 1 receptors knockout mice generated on a CD1 background displayed decreased ethanol-induced conditioned place preference (CPP) compared to wild-type (CB 1 þ / þ ) mice. Ethanol (0.5, 1.0, 1.5, and 2.0 g/kg) induced significant CPP in CB 1 þ / þ mice at all doses tested, whereas it induced significant CPP only at the highest dose of ethanol (2.0 g/kg) in CB 1 À/À mice.However, there was no genotypic difference in cocaine (20 mg/kg)-induced CPP. There was also no genotypic difference, neither in cocaine (10-50 mg/kg) nor in D-amphetamine (1.2-5 mg/kg)-induced locomotor effects. In addition, mutant and wild-type mice did not differ in sensitivity to the anxiolytic effects of ethanol (1.5 g/kg) when tested using the elevated plus maze. Interestingly, this decrease in ethanol efficacy to induce CPP in CB 1 À/À mice was correlated with an increase in D2/D3 receptors, as determined by [ 3 H]raclopride binding, whereas there was no difference in D1-like receptors, as determined by [ 3 H]SCH23390 binding, measured in the striatum from drug-naïve mice. This increase in D2/D3 binding sites observed in CB 1 knockout mice was associated with an altered locomotor response to the D2/D3 agonist quinpirole (low doses 0.02-0.1 mg/kg) but not to an alteration of quinpirole (0.1-1.0 mg/kg)-induced CPP compared to wild-type mice. Altogether, the present results indicate that lifelong deletion of CB 1 receptors reduced ethanol-induced CPP and that these reduced rewarding effects of ethanol are correlated to an overexpression of striatal dopamine D2 receptors.

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Experimental anxiety and the reinforcing effects of ethanol in rats

Cited by 24 publications

References 22 publications

Female Rats Display Enhanced Rewarding Effects of Ethanol That Are Hormone Dependent

Female Rats Display Enhanced Rewarding Effects of Ethanol That Are Hormone Dependent

Comparison of voluntary ethanol intake by two pairs of rat lines used as genetic models of anxiety

CB1 Receptor Knockout Mice Display Reduced Ethanol-Induced Conditioned Place Preference and Increased Striatal Dopamine D2 Receptors

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