The effects of tropicamide on mydriasis in young rats exhibiting a natural deficit in passive-avoidance responding.
The young rat at post-natal day 18-22 exhibits a natural deficit in passive-avoidance responding that can be corrected with the acute systemic administration of different cholinomimetic drugs, such as tacrine. In order to evaluate the generality of this apparent cholinergic hypofunction, different doses of the anticholinergic agent tropicamide, were administered either systemically or dropped directly into the eye of young or adult rats. Tropicamide produced mydriasis in a dose-dependent manner. The ED50 for tropicamide dropped into the eye was 0.025% for adult rats and 0.12% for young rats. When doses between 0.3 and 100 mg/kg were delivered systemically, the mean time course for recovery to baseline pupil size was accelerated in young rats. The average time to recovery across all doses was 112 +/- 27 min (mean+/-SE) for young rats and 274 +/- 70 min for adults. When subcutaneous tacrine was given immediately to young rats after training in a passive-avoidance response (PAR) task, retention was enhanced at testing 24 hours later in a dose-dependent manner. The response latencies were statistically different from saline-treated controls at doses of 0.003 and 0.01 mg/kg. This was not observed in adult rats. Taken together these results suggest that the PAR, along with the mydriacyl response of the young rat to tropicamide, may be regulated by a system of subsensitive cholinergic receptors.
Smith
R D
RD
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Grzelak
M E
ME
Belanger
B
B
Morgan
C A
CA
D000375:Aging / Q000502:physiology*; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D018727:Muscarinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D015878:Mydriasis / Q000139:chemically induced / Q000503:physiopathology*; D009883:Ophthalmic Solutions; D051381:Rats; D017207:Rats, Sprague-Dawley; D013619:Tacrine / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D014331:Tropicamide / Q000008:administration & dosage / Q000494:pharmacology*
D018727:Muscarinic Antagonists; D009883:Ophthalmic Solutions; D013619:Tacrine; D014331:Tropicamide