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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) Preference delta for the CS+ compartment (mean ± s.e.m) of mice conditioned with 2.2 g/kg ethanol from Experiment 2 extinction protocol (n = 47) and no extinction protocol (n = 61) in the habituation (Hab), post-conditioning test (Post-cond), environmental reinstatement (EnvR) and ethanol “priming” reinstatement (EtOHR). Preference delta was obtained through the percentage of total test time spent in the CS+ compartment minus the percentage of total test time spent in the CS- compartment in each test. *Significantly higher preference delta than in habituation test (P < 0.05). #Significantly higher preference than the extinction group in the same test (P < 0.001). (B) Pearson's correlation (r = 0.76, P < 0.05) between the preference delta in the post-conditioning test and the number of days required to return to the 95% confidence interval of preference delta habituation levels in the ethanol-conditioned mice (extinction protocol). (C) Pearson's correlation (r = 0.50, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the ethanol reinstatement test of ethanol-conditioned mice (extinction protocol). (D) Pearson's correlation (r = 0.42, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the environment reinstatement test in the ethanol-conditioned mice (no extinction protocol). (E) Pearson's correlation (r = 0.39, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the ethanol reinstatement test in ethanol-conditioned mice (no extinction protocol). 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 1: (A) Preference delta for the CS+ compartment (mean ± s.e.m) of mice conditioned with 2.2 g/kg ethanol from Experiment 2 extinction protocol (n = 47) and no extinction protocol (n = 61) in the habituation (Hab), post-conditioning test (Post-cond), environmental reinstatement (EnvR) and ethanol “priming” reinstatement (EtOHR). Preference delta was obtained through the percentage of total test time spent in the CS+ compartment minus the percentage of total test time spent in the CS- compartment in each test. *Significantly higher preference delta than in habituation test (P < 0.05). #Significantly higher preference than the extinction group in the same test (P < 0.001). (B) Pearson's correlation (r = 0.76, P < 0.05) between the preference delta in the post-conditioning test and the number of days required to return to the 95% confidence interval of preference delta habituation levels in the ethanol-conditioned mice (extinction protocol). (C) Pearson's correlation (r = 0.50, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the ethanol reinstatement test of ethanol-conditioned mice (extinction protocol). (D) Pearson's correlation (r = 0.42, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the environment reinstatement test in the ethanol-conditioned mice (no extinction protocol). (E) Pearson's correlation (r = 0.39, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the ethanol reinstatement test in ethanol-conditioned mice (no extinction protocol). 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: In order to compare the preference delta during the habituation, post-conditioning, environmental and ethanol “priming” reinstatement tests, we conducted a repeated measures ANOVA, with ethanol-conditioned mice from both protocols (extinction and no extinction) as the group factor (Figure 1A). Significant effects of group [F(1, 106) = 4.86, P < 0.05], tests [F(3, 318) = 13.19, P < 0.001] and interaction between group and tests factors [F(3, 318) = 4.05, P < 0.01] were observed. In both groups, a post-hoc analysis detected significantly higher preference for the CS+ compartment in the post-conditioning test than in the habituation (p < 0.05). No differences were observed among habituation, environmental and ethanol priming reinstatement tests in the extinction group (Figure 1A). Thus, there was no reinstatement of conditioned behavior after the extinction tests. On the other hand, in the no extinction group we observed higher levels of preference for the CS+ compartment in the ethanol reinstatement test than in the habituation and in the environmental reinstatement tests (P < 0.001), at similar levels to those from the post-conditioning test (Figure 1A). In this case, the priming dose of ethanol was able to reinstate the conditioned behavior. Indeed, in the ethanol priming reinstatement test animals from the no extinction group had a significantly higher preference than those from the extinction group (P < 0.001). The extinction protocol prevented the ethanol-induced reinstatement behavior in those mice repeatedly exposed to the CPP apparatus, but not in those left in their home cages during the withdrawal period.


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) Preference delta for the CS+ compartment (mean ± s.e.m) of mice conditioned with 2.2 g/kg ethanol from Experiment 2 extinction protocol (n = 47) and no extinction protocol (n = 61) in the habituation (Hab), post-conditioning test (Post-cond), environmental reinstatement (EnvR) and ethanol “priming” reinstatement (EtOHR). Preference delta was obtained through the percentage of total test time spent in the CS+ compartment minus the percentage of total test time spent in the CS- compartment in each test. *Significantly higher preference delta than in habituation test (P < 0.05). #Significantly higher preference than the extinction group in the same test (P < 0.001). (B) Pearson's correlation (r = 0.76, P < 0.05) between the preference delta in the post-conditioning test and the number of days required to return to the 95% confidence interval of preference delta habituation levels in the ethanol-conditioned mice (extinction protocol). (C) Pearson's correlation (r = 0.50, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the ethanol reinstatement test of ethanol-conditioned mice (extinction protocol). (D) Pearson's correlation (r = 0.42, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the environment reinstatement test in the ethanol-conditioned mice (no extinction protocol). (E) Pearson's correlation (r = 0.39, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the ethanol reinstatement test in ethanol-conditioned mice (no extinction protocol). 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

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

Figure 1: (A) Preference delta for the CS+ compartment (mean ± s.e.m) of mice conditioned with 2.2 g/kg ethanol from Experiment 2 extinction protocol (n = 47) and no extinction protocol (n = 61) in the habituation (Hab), post-conditioning test (Post-cond), environmental reinstatement (EnvR) and ethanol “priming” reinstatement (EtOHR). Preference delta was obtained through the percentage of total test time spent in the CS+ compartment minus the percentage of total test time spent in the CS- compartment in each test. *Significantly higher preference delta than in habituation test (P < 0.05). #Significantly higher preference than the extinction group in the same test (P < 0.001). (B) Pearson's correlation (r = 0.76, P < 0.05) between the preference delta in the post-conditioning test and the number of days required to return to the 95% confidence interval of preference delta habituation levels in the ethanol-conditioned mice (extinction protocol). (C) Pearson's correlation (r = 0.50, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the ethanol reinstatement test of ethanol-conditioned mice (extinction protocol). (D) Pearson's correlation (r = 0.42, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the environment reinstatement test in the ethanol-conditioned mice (no extinction protocol). (E) Pearson's correlation (r = 0.39, P < 0.05) between the preference delta in the post-conditioning test and the preference delta in the ethanol reinstatement test in ethanol-conditioned mice (no extinction protocol). 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: In order to compare the preference delta during the habituation, post-conditioning, environmental and ethanol “priming” reinstatement tests, we conducted a repeated measures ANOVA, with ethanol-conditioned mice from both protocols (extinction and no extinction) as the group factor (Figure 1A). Significant effects of group [F(1, 106) = 4.86, P < 0.05], tests [F(3, 318) = 13.19, P < 0.001] and interaction between group and tests factors [F(3, 318) = 4.05, P < 0.01] were observed. In both groups, a post-hoc analysis detected significantly higher preference for the CS+ compartment in the post-conditioning test than in the habituation (p < 0.05). No differences were observed among habituation, environmental and ethanol priming reinstatement tests in the extinction group (Figure 1A). Thus, there was no reinstatement of conditioned behavior after the extinction tests. On the other hand, in the no extinction group we observed higher levels of preference for the CS+ compartment in the ethanol reinstatement test than in the habituation and in the environmental reinstatement tests (P < 0.001), at similar levels to those from the post-conditioning test (Figure 1A). In this case, the priming dose of ethanol was able to reinstate the conditioned behavior. Indeed, in the ethanol priming reinstatement test animals from the no extinction group had a significantly higher preference than those from the extinction group (P < 0.001). The extinction protocol prevented the ethanol-induced reinstatement behavior in those mice repeatedly exposed to the CPP apparatus, but not in those left in their home cages during the withdrawal period.

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