Tacrine-scopolamine interactions on state-dependent retrieval.
OBJECTIVE
This study examined the effects of tacrine on scopolamine-induced state-dependence.


METHODS
Rats were trained to complete an FR10 schedule of lever presses for milk reward within 120 s after the onset of an operant session and were subsequently tested for the retrieval of the response in either the same or a different, pharmacologically defined, state.


RESULTS
In rats trained with 2.5 mg/kg scopolamine, the pre-test administration of 10 mg/kg tacrine prevented scopolamine from enabling the retrieval that otherwise occurred when animals were both trained and tested with scopolamine. However, retrieval of the response was also hampered in animals that were trained with tacrine-scopolamine co-administration and tested with saline, and vice versa, indicating that the co-administration of tacrine and scopolamine did not induce the saline-associated, presumably normal state. At >/=2.5 mg/kg doses, tacrine itself induced state-dependence with both tacrine-to-saline and saline-to-tacrine state changes.


CONCLUSIONS
The findings indicate that tacrine is unable to normalize the particular mnesic state induced by scopolamine. The data may elucidate tacrine's limited therapeutic efficacy insofar as scopolamine's mnesic actions both model human pathology and are due to scopolamine producing state-dependence.
Bruins Slot
Liesbeth A
LA
Centre de Recherche Pierre Fabre, 17 avenue Jean Moulin, 81106 Castres Cedex, France.
Chopin
Philippe
P
Colpaert
Francis C
FC
D000704:Analysis of Variance; D000818:Animals; D003216:Conditioning, Operant / Q000187:drug effects* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D008297:Male; D008568:Memory / Q000187:drug effects*; D018727:Muscarinic Antagonists / Q000494:pharmacology; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012601:Scopolamine / Q000494:pharmacology*; D013619:Tacrine / Q000494:pharmacology*
D018727:Muscarinic Antagonists; D013619:Tacrine; D012601:Scopolamine