Biomedical subjects

R D Shytle

Publications and source records attributed to R D Shytle.

21 records · Page 2Linked to original sources

PubMed1995

(-)-nicotine protects against systemic kainic acid-induced excitotoxic effects.

(-)-Nicotine was shown to produce in vivo protection against neurobehavioral effects caused by systemically administered kainic acid (KA), an excitotoxin that has been widely used to induce temporal lobe convulsions including "wet dog shakes" in experimental animals. Rats pretreated with (-)-nicotine (0.5 mg/kg sc) 15 min before receiving KA (12.0 mg/kg sc) exhibited a marked reduction (P < 0.5) in the number of wet dog shakes when compared to saline-pretreated rats. Similarly, little visible brain damage was found in the (-)-nicotine-pretreated rats, but a widespread reduction in acetylcholinesterase-positive neurons was noted in the hippocampal areas of the saline-pretreated animals. While the mechanism of neuroprotection of (-)-nicotine is still not known, these findings suggest that (-)-nicotine may act as a therapeutic agent for putative excitotoxin-mediated disorders.

Animals↗

PubMed1995

Striatal dopamine-mediated motor behavior is altered following occlusion of the middle cerebral artery.

Cerebral infarct (stroke) causes striatal damage with subsequent deterioration of sensorimotor and cognitive functions that may be mediated by the dopamine receptor system. In the present study, transient, focal ischemia was induced in Sprague-Dawley rats by middle cerebral artery occlusion. Ischemic animals exhibited significantly less dopamine antagonist (haloperidol)-induced catalepsy and more dopamine agonist (amphetamine)-induced hyperactivity than sham-operated animals. Younger ischemic animals showed more profound behavioral alteration but also displayed greater recovery over time than older ischemic animals. Histologic data revealed a lateral striatal lesion in all ischemic animals. These results place the striatal dopaminergic system as a possible strategic venue for the treatment of cerebral ischemia. In addition, aging is found to be a risk factor for stroke as noted in humans.

Animals↗

PubMed1995

Nicotine blocks kainic acid-induced wet dog shakes in rats.

Systemic or central administration of kainic acid (KA) in rats results in the expression of wet dog shakes (WDS) followed by motoric seizures and convulsions, which are associated with limbic neurotoxicity. Although a number of neurotransmitter systems are thought to be involved with this KA-induced syndrome, little is known about the possible influence of cholinergic nicotinic receptor modulation. In the study presented here, we pretreated rats with saline or 0.5 mg/kg nicotine base followed 15 minutes later by 12.0 mg/kg KA and then observed the incidence of WDS between 45 and 120 minutes post-KA injection. Rats pretreated with nicotine exhibited significantly less WDS than those pretreated with saline (p < .001). Whereas the mechanism for this nicotine effect is currently not known, future experiments will look at dose-response relationships, the role of nicotine receptors, and possible neuroprotective potential of nicotine in this KA-induced syndrome.

Animals↗