Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2008 Jul;29(7):1060-9.
doi: 10.1016/j.neurobiolaging.2007.02.003. Epub 2007 Mar 23.

Beta2 Adrenergic Agonist, Clenbuterol, Enhances Working Memory Performance in Aging Animals

Affiliations
Free PMC article

Beta2 Adrenergic Agonist, Clenbuterol, Enhances Working Memory Performance in Aging Animals

Brian P Ramos et al. Neurobiol Aging. .
Free PMC article

Abstract

Previous studies using a mixed beta1 and beta2 adrenergic antagonist, propanolol, have indicated that beta adrenoceptors have little effect on the cognitive functioning of the prefrontal cortex. However, recent studies have suggested that endogenous stimulation of beta1 adrenoceptors impairs working memory in both rats and monkeys. Since propanolol has no effect on cognition, we hypothesized that activation of beta2 adrenoceptors might improve performance in a working memory task. We tested this hypothesis by observing the effects of the beta2 agonist, clenbuterol, on spatial working memory performance. Clenbuterol was either infused directly into the prefrontal cortex (rats) or administered systemically (monkeys). Results demonstrated that clenbuterol improved performance in many young and aged rats and monkeys who performed poorly under control conditions. Actions at beta2 adrenoceptors were confirmed by challenging the clenbuterol response with the beta2 adrenergic antagonist, ICI 118,551. The effects of clenbuterol were not universal and depended on the cognitive status of the animal: the drug moderately improved only a subset of animals with working memory impairment.

Conflict of interest statement

Disclosure

None of the authors have any actual or potential conflicts of interest that could inappropriately influence (bias) this study.

Figures

Fig. 1
Fig. 1
Location of cannula tips in the rat medial PFC (prelimbic cortex). All bilateral infusions of 0.5 µL occurred at 4.5 mm DV. Coronal slices indicate distance (mm) anterior from bregma.
Fig. 2
Fig. 2
Differences in baseline performance contribute to the effects seen with a β2 adrenergic agonist. Clenbuterol (0.1 µg/0.5 µL) improves performance in the delayed alternation task in a T-maze when compared to performance following a vehicle treatment in both young and aged rats with prefrontal cortical deficits (low baseline). However, clenbuterol had no effect when infused into the PFC of high baseline young rats. Results represent mean ± S.E.M. percent correct. *p = 0.0001; **p = 0.004.
Fig. 3
Fig. 3
Clenbuterol’s beneficial effects on working memory performance of young rats are blocked by ICI 118,551. Clenbuterol (0.1 µg/0.5 µL) improves rats’ performance in the delayed alternation task in a T-maze when compared to performance following a vehicle treatment. Blockade of β2 adrenoceptors with ICI 118,551 (0.0001 µg/0.5 µL) reverses the beneficial effects of clenbuterol. Results represent mean ± S.E.M. percent correct, n = 9. *p = 0.02; **p = 0.009.
Fig. 4
Fig. 4
Clenbuterol dose response curve. Systemic administration of clenbuterol does not have a significant effect on working memory performance when all of the monkeys in the study are examined. Dashed line indicates the mean performance after saline treatment (19.93 ± 0.18). Results represent mean ± S.E.M. correct out of 30 trials, n = 10.
Fig. 5
Fig. 5
Clenbuterol’s beneficial effects on working memory performance of a subset of monkeys are blocked by ICI 118,551. Systemic administration of the best effective dose of clenbuterol (0.0001–0.01 mg/kg) improves the monkey’s performance in the delayed response task when compared to performance following a vehicle treatment. Similar to the rat studies, blockade of β2 adrenoceptors, at a dose that has no effects on its own (0.0001–0.01 mg/kg), reverses clenbuterol’s beneficial effects on working memory performance. Results represent mean ± S.E.M. percent correct, n = 5. *p = 0.01; **p = 0.02.

Similar articles

See all similar articles

Cited by 22 articles

See all "Cited by" articles

Publication types

Substances

Feedback