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Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats.

Winsauer PJ, Filipeanu CM, Weed PF, Sutton JL - Front Pharmacol (2015)

Bottom Line: Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic Δ(9)-THC, all of the Δ(9)-THC groups developed tolerance.However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic Δ(9)-THC was initiated.These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center New Orleans New Orleans, LA, USA ; Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center New Orleans New Orleans, LA, USA.

ABSTRACT
The effects of hormone status and age on the development of tolerance to Δ(9)-THC were assessed in sham-operated (intact) or ovariectomized (OVX) female rats that received either intraperitoneal saline or 5.6 mg/kg of Δ(9)-THC daily from postnatal day (PD) 75-180 (early adulthood onward) or PD 35-140 (adolescence onward). During this time, the four groups for each age (i.e., intact/saline, intact/THC, OVX/saline, and OVX/THC) were trained in a learning and performance procedure and dose-effect curves were established for Δ(9)-THC (0.56-56 mg/kg) and the cannabinoid type-1 receptor (CB1R) antagonist rimonabant (0.32-10 mg/kg). Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic Δ(9)-THC, all of the Δ(9)-THC groups developed tolerance. However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic Δ(9)-THC was initiated. There was no evidence of dependence in any of the groups. Hippocampal protein expression of CB1R, AHA1 (a co-chaperone of CB1R) and HSP90β (a molecular chaperone modulated by AHA-1) was affected more by OVX than chronic Δ(9)-THC; striatal protein expression was not consistently affected by either manipulation. Hippocampal brain-derived neurotrophic factor expression varied with age, hormone status, and chronic treatment. Thus, hormonal status differentially affects the development of tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning and performance behavior in adolescent, but not adult, female rats. These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity.

No MeSH data available.


Related in: MedlinePlus

Acute effects of rimonabant in intact and OVX females that received either saline (A) or 5.6 mg/kg of Δ9-THC (B) daily from adolescence or early adulthood to sacrifice and that were responding under an acquisition and performance procedure. The data for the two age groups were combined as there was no marked difference between these age groups. Data points and vertical lines above C in each panel indicate the grand mean and SEM for 3–10 vehicle (control) injections administered to each subject in each treatment group. In the upper panels (response rate), asterisks alone or in combination with brackets indicate significant differences between particular doses of Δ9-THC and acute saline (control) injections, whereas crosses indicate a significant difference from the intact/saline group under control conditions or after particular doses of rimonabant. In the bottom panels (percent errors), there were no significant interactions, only main effects for dose and treatment group. Therefore, the asterisks with brackets indicate significant differences from control injections for all of the groups at every dose of rimonabant, whereas the crosses with brackets indicate the treatment groups that were significantly different from the intact/saline group irrespective of dose.
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Figure 5: Acute effects of rimonabant in intact and OVX females that received either saline (A) or 5.6 mg/kg of Δ9-THC (B) daily from adolescence or early adulthood to sacrifice and that were responding under an acquisition and performance procedure. The data for the two age groups were combined as there was no marked difference between these age groups. Data points and vertical lines above C in each panel indicate the grand mean and SEM for 3–10 vehicle (control) injections administered to each subject in each treatment group. In the upper panels (response rate), asterisks alone or in combination with brackets indicate significant differences between particular doses of Δ9-THC and acute saline (control) injections, whereas crosses indicate a significant difference from the intact/saline group under control conditions or after particular doses of rimonabant. In the bottom panels (percent errors), there were no significant interactions, only main effects for dose and treatment group. Therefore, the asterisks with brackets indicate significant differences from control injections for all of the groups at every dose of rimonabant, whereas the crosses with brackets indicate the treatment groups that were significantly different from the intact/saline group irrespective of dose.

Mentions: Given that separate analyses indicated that there were only minor differences in the effects of rimonabant for the groups that initiated Δ9-THC during adolescence and early adulthood, the data for the two ages were combined. As shown in Figure 5, rimonabant (0.32–10 mg/kg) produced relatively consistent rate-decreasing and error-increasing effects in all four treatment groups. However, rimonabant affected response rate and percent errors differently. For response rate, differences in the potency of rimonabant’s effects were reflected by significant dose × treatment interactions in both the acquisition [F(12,144) = 3.58, p < 0.001] and performance [F(12,144) = 3.52, p < 0.001] components, along with significant main effects of treatment [acquisition: F(3,144) = 4.04, p = 0.014, performance: F(3,144) = 3.24, p = 0.033] and rimonabant dose [acquisition: F(4,144) = 74.93, p < 0.001, performance: F(4,144) = 54.19, p < 0.001]. In contrast, for percent error, there were no differences in potency among the groups, as there were only main effects of treatment [acquisition: F(3,135) = 6.08, p = 0.002, performance: F(3,138) = 6.78, p < 0.001] and rimonabant dose [acquisition: F(4,135) = 39.49, p < 0.001, performance: F(4,138) = 18.82, p < 0.001]; the dose × treatment interactions were not significant for responding in either component [acquisition: F(12,135) = 0.75, p > 0.05, performance: F(12,138) = 0.65, p > 0.05].


Hormonal status and age differentially affect tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning in female rats.

Winsauer PJ, Filipeanu CM, Weed PF, Sutton JL - Front Pharmacol (2015)

Acute effects of rimonabant in intact and OVX females that received either saline (A) or 5.6 mg/kg of Δ9-THC (B) daily from adolescence or early adulthood to sacrifice and that were responding under an acquisition and performance procedure. The data for the two age groups were combined as there was no marked difference between these age groups. Data points and vertical lines above C in each panel indicate the grand mean and SEM for 3–10 vehicle (control) injections administered to each subject in each treatment group. In the upper panels (response rate), asterisks alone or in combination with brackets indicate significant differences between particular doses of Δ9-THC and acute saline (control) injections, whereas crosses indicate a significant difference from the intact/saline group under control conditions or after particular doses of rimonabant. In the bottom panels (percent errors), there were no significant interactions, only main effects for dose and treatment group. Therefore, the asterisks with brackets indicate significant differences from control injections for all of the groups at every dose of rimonabant, whereas the crosses with brackets indicate the treatment groups that were significantly different from the intact/saline group irrespective of dose.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4488627&req=5

Figure 5: Acute effects of rimonabant in intact and OVX females that received either saline (A) or 5.6 mg/kg of Δ9-THC (B) daily from adolescence or early adulthood to sacrifice and that were responding under an acquisition and performance procedure. The data for the two age groups were combined as there was no marked difference between these age groups. Data points and vertical lines above C in each panel indicate the grand mean and SEM for 3–10 vehicle (control) injections administered to each subject in each treatment group. In the upper panels (response rate), asterisks alone or in combination with brackets indicate significant differences between particular doses of Δ9-THC and acute saline (control) injections, whereas crosses indicate a significant difference from the intact/saline group under control conditions or after particular doses of rimonabant. In the bottom panels (percent errors), there were no significant interactions, only main effects for dose and treatment group. Therefore, the asterisks with brackets indicate significant differences from control injections for all of the groups at every dose of rimonabant, whereas the crosses with brackets indicate the treatment groups that were significantly different from the intact/saline group irrespective of dose.
Mentions: Given that separate analyses indicated that there were only minor differences in the effects of rimonabant for the groups that initiated Δ9-THC during adolescence and early adulthood, the data for the two ages were combined. As shown in Figure 5, rimonabant (0.32–10 mg/kg) produced relatively consistent rate-decreasing and error-increasing effects in all four treatment groups. However, rimonabant affected response rate and percent errors differently. For response rate, differences in the potency of rimonabant’s effects were reflected by significant dose × treatment interactions in both the acquisition [F(12,144) = 3.58, p < 0.001] and performance [F(12,144) = 3.52, p < 0.001] components, along with significant main effects of treatment [acquisition: F(3,144) = 4.04, p = 0.014, performance: F(3,144) = 3.24, p = 0.033] and rimonabant dose [acquisition: F(4,144) = 74.93, p < 0.001, performance: F(4,144) = 54.19, p < 0.001]. In contrast, for percent error, there were no differences in potency among the groups, as there were only main effects of treatment [acquisition: F(3,135) = 6.08, p = 0.002, performance: F(3,138) = 6.78, p < 0.001] and rimonabant dose [acquisition: F(4,135) = 39.49, p < 0.001, performance: F(4,138) = 18.82, p < 0.001]; the dose × treatment interactions were not significant for responding in either component [acquisition: F(12,135) = 0.75, p > 0.05, performance: F(12,138) = 0.65, p > 0.05].

Bottom Line: Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic Δ(9)-THC, all of the Δ(9)-THC groups developed tolerance.However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic Δ(9)-THC was initiated.These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center New Orleans New Orleans, LA, USA ; Alcohol and Drug Abuse Center of Excellence, Louisiana State University Health Sciences Center New Orleans New Orleans, LA, USA.

ABSTRACT
The effects of hormone status and age on the development of tolerance to Δ(9)-THC were assessed in sham-operated (intact) or ovariectomized (OVX) female rats that received either intraperitoneal saline or 5.6 mg/kg of Δ(9)-THC daily from postnatal day (PD) 75-180 (early adulthood onward) or PD 35-140 (adolescence onward). During this time, the four groups for each age (i.e., intact/saline, intact/THC, OVX/saline, and OVX/THC) were trained in a learning and performance procedure and dose-effect curves were established for Δ(9)-THC (0.56-56 mg/kg) and the cannabinoid type-1 receptor (CB1R) antagonist rimonabant (0.32-10 mg/kg). Despite the persistence of small rate-decreasing and error-increasing effects in intact and OVX females from both ages during chronic Δ(9)-THC, all of the Δ(9)-THC groups developed tolerance. However, the magnitude of tolerance, as well as the effect of hormone status, varied with the age at which chronic Δ(9)-THC was initiated. There was no evidence of dependence in any of the groups. Hippocampal protein expression of CB1R, AHA1 (a co-chaperone of CB1R) and HSP90β (a molecular chaperone modulated by AHA-1) was affected more by OVX than chronic Δ(9)-THC; striatal protein expression was not consistently affected by either manipulation. Hippocampal brain-derived neurotrophic factor expression varied with age, hormone status, and chronic treatment. Thus, hormonal status differentially affects the development of tolerance to the disruptive effects of delta-9-tetrahydrocannabinol (Δ(9)-THC) on learning and performance behavior in adolescent, but not adult, female rats. These factors and their interactions also differentially affect cannabinoid signaling proteins in the hippocampus and striatum, and ultimately, neural plasticity.

No MeSH data available.


Related in: MedlinePlus