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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 Experiments 1–3A in the habituation and post-conditioning test classified as aversion (n = 32), low preference (n = 57) or high preference (n = 65) according to the classification model based on the preference delta. *Differs from the other groups in the same test. #Differs from the habituation test (P < 0.001). (B) Preference delta for the CS+ compartment in the extinction tests phase of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion (n = 12), low preference (n = 20) and high preference (n = 15). *Differs from the aversion group in the same test (P < 0. 05). #Differs from the low preference group in the same test (P < 0. 05). (C) Number of days required for the conditioned behavior to be extinguished (mean ± s.e.m) of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion, low preference and high preference. *Differs from other groups (P < 0.01). (D) Preference delta for the CS+ compartment of ethanol-conditioned mice in the environmental (EnvR) and ethanol reinstatement (EtOHR) tests of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion, low preference and high preference. *Higher than other groups in the same test (P < 0.001). (E) Preference delta for the CS+ compartment in the environmental and ethanol reinstatement tests of ethanol-conditioned mice (Experiment 2 no extinction protocol) classified as aversion (n = 9), low preference (n = 21) and high preference (n = 31). *Differs from the aversion group in the same test (P < 0.01). Not all significant differences between tests are depicted in this figure. See text for details.
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Figure 2: (A) Preference delta for the CS+ compartment (mean ± s.e.m) of mice conditioned with 2.2 g/kg ethanol from Experiments 1–3A in the habituation and post-conditioning test classified as aversion (n = 32), low preference (n = 57) or high preference (n = 65) according to the classification model based on the preference delta. *Differs from the other groups in the same test. #Differs from the habituation test (P < 0.001). (B) Preference delta for the CS+ compartment in the extinction tests phase of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion (n = 12), low preference (n = 20) and high preference (n = 15). *Differs from the aversion group in the same test (P < 0. 05). #Differs from the low preference group in the same test (P < 0. 05). (C) Number of days required for the conditioned behavior to be extinguished (mean ± s.e.m) of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion, low preference and high preference. *Differs from other groups (P < 0.01). (D) Preference delta for the CS+ compartment of ethanol-conditioned mice in the environmental (EnvR) and ethanol reinstatement (EtOHR) tests of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion, low preference and high preference. *Higher than other groups in the same test (P < 0.001). (E) Preference delta for the CS+ compartment in the environmental and ethanol reinstatement tests of ethanol-conditioned mice (Experiment 2 no extinction protocol) classified as aversion (n = 9), low preference (n = 21) and high preference (n = 31). *Differs from the aversion group in the same test (P < 0.01). Not all significant differences between tests are depicted in this figure. See text for details.

Mentions: We ran complementary statistical analyses with the CPP variables considering the classification model proposed above (see Figure 2). Repeated measures ANOVA with groups (aversion, low preference and high preference) as the independent factor detected significant effects of group [F(2, 151) = 221.49, P < 0.001], tests [F(1, 151) = 89.11, P < 0.001] and interaction between group and tests factors [F(1, 151) = 144.91, P < 0.001]. While the preference delta in the post-conditioning test of the aversion group was lower than in the habituation, both low and high preference groups' preference deltas were higher in the post-conditioning test than their own levels in the habituation (P < 0.001). In the post-conditioning test all groups were significantly different from each other: while the aversion group presented a negative preference, the high preference group presented the highest preference (P < 0.001) (Figure 2A). These results indicate that the classification method was effective to differentiate the three groups according to their ethanol conditioned behavior.


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 Experiments 1–3A in the habituation and post-conditioning test classified as aversion (n = 32), low preference (n = 57) or high preference (n = 65) according to the classification model based on the preference delta. *Differs from the other groups in the same test. #Differs from the habituation test (P < 0.001). (B) Preference delta for the CS+ compartment in the extinction tests phase of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion (n = 12), low preference (n = 20) and high preference (n = 15). *Differs from the aversion group in the same test (P < 0. 05). #Differs from the low preference group in the same test (P < 0. 05). (C) Number of days required for the conditioned behavior to be extinguished (mean ± s.e.m) of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion, low preference and high preference. *Differs from other groups (P < 0.01). (D) Preference delta for the CS+ compartment of ethanol-conditioned mice in the environmental (EnvR) and ethanol reinstatement (EtOHR) tests of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion, low preference and high preference. *Higher than other groups in the same test (P < 0.001). (E) Preference delta for the CS+ compartment in the environmental and ethanol reinstatement tests of ethanol-conditioned mice (Experiment 2 no extinction protocol) classified as aversion (n = 9), low preference (n = 21) and high preference (n = 31). *Differs from the aversion group in the same test (P < 0.01). Not all significant differences between tests are depicted in this figure. See text for details.
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Related In: Results  -  Collection

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Figure 2: (A) Preference delta for the CS+ compartment (mean ± s.e.m) of mice conditioned with 2.2 g/kg ethanol from Experiments 1–3A in the habituation and post-conditioning test classified as aversion (n = 32), low preference (n = 57) or high preference (n = 65) according to the classification model based on the preference delta. *Differs from the other groups in the same test. #Differs from the habituation test (P < 0.001). (B) Preference delta for the CS+ compartment in the extinction tests phase of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion (n = 12), low preference (n = 20) and high preference (n = 15). *Differs from the aversion group in the same test (P < 0. 05). #Differs from the low preference group in the same test (P < 0. 05). (C) Number of days required for the conditioned behavior to be extinguished (mean ± s.e.m) of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion, low preference and high preference. *Differs from other groups (P < 0.01). (D) Preference delta for the CS+ compartment of ethanol-conditioned mice in the environmental (EnvR) and ethanol reinstatement (EtOHR) tests of ethanol-conditioned mice (Experiment 2 extinction protocol) classified as aversion, low preference and high preference. *Higher than other groups in the same test (P < 0.001). (E) Preference delta for the CS+ compartment in the environmental and ethanol reinstatement tests of ethanol-conditioned mice (Experiment 2 no extinction protocol) classified as aversion (n = 9), low preference (n = 21) and high preference (n = 31). *Differs from the aversion group in the same test (P < 0.01). Not all significant differences between tests are depicted in this figure. See text for details.
Mentions: We ran complementary statistical analyses with the CPP variables considering the classification model proposed above (see Figure 2). Repeated measures ANOVA with groups (aversion, low preference and high preference) as the independent factor detected significant effects of group [F(2, 151) = 221.49, P < 0.001], tests [F(1, 151) = 89.11, P < 0.001] and interaction between group and tests factors [F(1, 151) = 144.91, P < 0.001]. While the preference delta in the post-conditioning test of the aversion group was lower than in the habituation, both low and high preference groups' preference deltas were higher in the post-conditioning test than their own levels in the habituation (P < 0.001). In the post-conditioning test all groups were significantly different from each other: while the aversion group presented a negative preference, the high preference group presented the highest preference (P < 0.001) (Figure 2A). These results indicate that the classification method was effective to differentiate the three groups according to their ethanol conditioned behavior.

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