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Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses.

Pildervasser JV, Abrahao KP, Souza-Formigoni ML - Front Behav Neurosci (2014)

Bottom Line: Conditioned place preference (CPP) is a model to study the role of drug conditioning properties.Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period.Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished.

View Article: PubMed Central - PubMed

Affiliation: Unidade de Dependência de Drogas, Departament of Psicobiologia, Universidade Federal de Sao Paulo Sao Paulo, Brazil.

ABSTRACT
Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties.

No MeSH data available.


Related in: MedlinePlus

(A) Locomotor activity (mean ± s.e.m) for 15 min of mice treated with saline (SAL) (n = 9) or 2.2 g/kg ethanol (NSENS = 8; SENS = 8) in the novelty-exposure test and in tests 1–4 (Experiment 3A). Based on their activity in test 4, the ethanol-treated mice were classified as “sensitized” or “non-sensitized.” *Higher than SAL and NSENS groups on the same test (P < 0.05) and higher than their own levels in test 1 (P < 0.05). (B) Preference delta for the CS+ compartment (mean ± s.e.m) in the post-conditioning test of ethanol-conditioned mice (Experiment 3A) classified as saline (SAL), “non sensitized” (NSENS) and “sensitized” (SENS) in the behavioral sensitization protocol. (C) Pearson's correlation (r = 0.11, P > 0.05) between the preference delta in the post-conditioning test and the locomotor activity on test 4 of ethanol-treated mice. Each point represents a single animal classified according to its preference for the CS+ compartment, determined by the classification model described in the text (See Table 1).
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Figure 3: (A) Locomotor activity (mean ± s.e.m) for 15 min of mice treated with saline (SAL) (n = 9) or 2.2 g/kg ethanol (NSENS = 8; SENS = 8) in the novelty-exposure test and in tests 1–4 (Experiment 3A). Based on their activity in test 4, the ethanol-treated mice were classified as “sensitized” or “non-sensitized.” *Higher than SAL and NSENS groups on the same test (P < 0.05) and higher than their own levels in test 1 (P < 0.05). (B) Preference delta for the CS+ compartment (mean ± s.e.m) in the post-conditioning test of ethanol-conditioned mice (Experiment 3A) classified as saline (SAL), “non sensitized” (NSENS) and “sensitized” (SENS) in the behavioral sensitization protocol. (C) Pearson's correlation (r = 0.11, P > 0.05) between the preference delta in the post-conditioning test and the locomotor activity on test 4 of ethanol-treated mice. Each point represents a single animal classified according to its preference for the CS+ compartment, determined by the classification model described in the text (See Table 1).

Mentions: The same group of mice went through a behavioral sensitization protocol 14 days after the post-conditioning test (Figure 3A). As previously described, mice were classified according to their locomotor activity on the last day of the sensitization protocol. Repeated measures ANOVA considering group (saline, non-sensitized and sensitized animals) as the independent factor detected significant effects of group [F(2, 22) = 25.25, P < 0.001], tests [F(3, 66) = 18.29, P < 0.001] and interaction between group and tests factors [F(6, 66) = 12.57, P < 0.001]. In test 4, the sensitized group presented significantly higher activity than the saline-treated animals (P < 0.01) and then their own levels in tests 1–3 (P < 0.05). Non-sensitized mice, presented similar activity levels as those observed in the saline group. Thus, mice classified as sensitized showed robust behavioral sensitization with progressive increase in the activity counts during ethanol treatment (P < 0.05), while the non-sensitized group did not. It is important to notice that there were no differences in baseline or acute (test 1) locomotor activity levels among saline, sensitized and non-sensitized groups.


Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses.

Pildervasser JV, Abrahao KP, Souza-Formigoni ML - Front Behav Neurosci (2014)

(A) Locomotor activity (mean ± s.e.m) for 15 min of mice treated with saline (SAL) (n = 9) or 2.2 g/kg ethanol (NSENS = 8; SENS = 8) in the novelty-exposure test and in tests 1–4 (Experiment 3A). Based on their activity in test 4, the ethanol-treated mice were classified as “sensitized” or “non-sensitized.” *Higher than SAL and NSENS groups on the same test (P < 0.05) and higher than their own levels in test 1 (P < 0.05). (B) Preference delta for the CS+ compartment (mean ± s.e.m) in the post-conditioning test of ethanol-conditioned mice (Experiment 3A) classified as saline (SAL), “non sensitized” (NSENS) and “sensitized” (SENS) in the behavioral sensitization protocol. (C) Pearson's correlation (r = 0.11, P > 0.05) between the preference delta in the post-conditioning test and the locomotor activity on test 4 of ethanol-treated mice. Each point represents a single animal classified according to its preference for the CS+ compartment, determined by the classification model described in the text (See Table 1).
© Copyright Policy - open-access
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4126182&req=5

Figure 3: (A) Locomotor activity (mean ± s.e.m) for 15 min of mice treated with saline (SAL) (n = 9) or 2.2 g/kg ethanol (NSENS = 8; SENS = 8) in the novelty-exposure test and in tests 1–4 (Experiment 3A). Based on their activity in test 4, the ethanol-treated mice were classified as “sensitized” or “non-sensitized.” *Higher than SAL and NSENS groups on the same test (P < 0.05) and higher than their own levels in test 1 (P < 0.05). (B) Preference delta for the CS+ compartment (mean ± s.e.m) in the post-conditioning test of ethanol-conditioned mice (Experiment 3A) classified as saline (SAL), “non sensitized” (NSENS) and “sensitized” (SENS) in the behavioral sensitization protocol. (C) Pearson's correlation (r = 0.11, P > 0.05) between the preference delta in the post-conditioning test and the locomotor activity on test 4 of ethanol-treated mice. Each point represents a single animal classified according to its preference for the CS+ compartment, determined by the classification model described in the text (See Table 1).
Mentions: The same group of mice went through a behavioral sensitization protocol 14 days after the post-conditioning test (Figure 3A). As previously described, mice were classified according to their locomotor activity on the last day of the sensitization protocol. Repeated measures ANOVA considering group (saline, non-sensitized and sensitized animals) as the independent factor detected significant effects of group [F(2, 22) = 25.25, P < 0.001], tests [F(3, 66) = 18.29, P < 0.001] and interaction between group and tests factors [F(6, 66) = 12.57, P < 0.001]. In test 4, the sensitized group presented significantly higher activity than the saline-treated animals (P < 0.01) and then their own levels in tests 1–3 (P < 0.05). Non-sensitized mice, presented similar activity levels as those observed in the saline group. Thus, mice classified as sensitized showed robust behavioral sensitization with progressive increase in the activity counts during ethanol treatment (P < 0.05), while the non-sensitized group did not. It is important to notice that there were no differences in baseline or acute (test 1) locomotor activity levels among saline, sensitized and non-sensitized groups.

Bottom Line: Conditioned place preference (CPP) is a model to study the role of drug conditioning properties.Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period.Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished.

View Article: PubMed Central - PubMed

Affiliation: Unidade de Dependência de Drogas, Departament of Psicobiologia, Universidade Federal de Sao Paulo Sao Paulo, Brazil.

ABSTRACT
Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties.

No MeSH data available.


Related in: MedlinePlus