Signs Of Cholinergic Stimulation Research Articles

Reversible and persistent decreases in cocaine self-administration after cholinesterase inhibition

We recently observed that pretreatment with the cholinesterase inhibitor, tacrine can produce long-lasting reductions in cocaine-reinforced behavior, described as persistent attenuation. In addition to inhibiting both acetylcholinesterase (AChE) and butyrylcholinesterase, tacrine can potentiate actions of dopamine. This study was carried out to evaluate the effects of donepezil (which selectively inhibits AChE) and rivastigmine (which inhibits both AChE and butyrylcholinesterase) on cocaine self-administration. High self-administration rats self-administered different doses of cocaine under a fixed ratio-5 schedule. Over a 4-day period, vehicle, donepezil, or rivastigmine was infused as animals were maintained in home cages (21 h per day), with signs of cholinergic stimulation (fasciculation, vacuous jaw movements, yawning, and diarrhea) scored by a blinded observer. Both compounds dose-dependently decreased cocaine self-administration, but differed in the potency and temporal pattern of their effects. Self-administration of low-dose cocaine was decreased to a greater degree by rivastigmine than donepezil (50% effective doses of 2.33 and 6.21 mg/kg/day, respectively), but this early effect did not continue beyond sessions immediately after treatment with rivastigmine. Group means for cocaine self-administration were decreased at some time points occurring between 1 and 3 days after the treatment with 10 mg/kg/day of donepezil (late effects), with decreases of more than 80% observed in some individual rats that persisted for 1 week or longer. Early, but not late, effects were correlated with signs of cholinergic stimulation. In summary, pretreatment with donepezil, but not rivastigmine produced persistent reductions in cocaine-reinforced behavior, which were not associated with signs of cholinergic stimulation.

Neonatal cholinesterase inhibitor poisoning: Materno‐fetal exchange of pesticide

This is a case report of a neonatal cholinesterase inhibitor poisoning after non-accidental ingestion of a carbamate containing pesticide by the mother prior to delivery. The mother presented with symptoms of cholinesterase inhibitor poisoning at 40 weeks of gestation. A fetal bradycardia was present. The mother improved after administration of intravenous atropine. Spontaneous labour ensued and a term female infant weighing 3200 g was delivered. The infant had signs of cholinergic stimulation and decreased levels of serum cholinesterase. The neonate presented with a marked tachycardia. The heart rate normalized after administration of atropine. Therefore, we concluded that the tachycardia was due to the cholinesterase inhibitor substance, causing catecholamine release by stimulation of nicotinic receptors. Another potential contributing factor to the tachycardia, although unlikely in our patient, was the atropine administered to the mother prior to delivery. Mother and infant recovered well. We conclude that infants can present with tachycardia associated with cholinesterase inhibitor toxicity. Despite the side-effects intravenous atropine should not be withheld in the treatment of mother and infant.

Influence of pregnancy on parathion toxicity and disposition

The effects of pregnancy and lactation on the toxicity and distribution of parathion and paraoxon were examined. Signs of cholinergic stimulation were more intense in pregnant mice when compared to virgin controls after administration of parathion or its active metabolite, paraoxon. Cholinesterase activity and tissue levels of parathion and paraoxon were determined in mice at 19 days of gestation or Day 19 postpartum after administration of a single dose of 5 mg/kg parathion or 0.58 mg/kg paraoxon. Plasma (pseudo) cholinesterase activity was consistently lower in treated pregnant mice. Total brain cholinesterase was also suppressed to a greater degree in pregnant mice after treatment with parathion or paraoxon when compared with virgin animals treated similarly. In addition, when equal quantities of paraoxon (32 μg) were administered to both pregnant and virgin animals, total brain cholinesterase was significantly less in pregnant mice. Administration of parathion to lactating mice on Day 19 postpartum did not result in any significant differences in plasma or brain cholinesterase activity when compared to that in virgin animals. Pregnant mice treated with 5 mg/kg parathion demonstrated higher concentrations of both parathion and paraoxon in blood and brain than similarly treated virgin controls which correlated with the enhanced cholinesterase inhibition. Decreased ability to detoxify paraoxon was also demonstrated by a significant reduction in serum paraoxonase activity during pregnancy.

Stimulation of Lachrymation and Salivation in the Adult Fowl (Gallus domesticus)

Summary An assessment was made of the efficacy of 5 cholinergic drugs (arecoline, carbachol, neostigmine, physostigmine and pilocarpine) in inducing lachrymation and salivation in 44 adult hens. While the drugs all produced signs of cholinergic stimulation, including secretory activity, the greatest lachrymal response was obtained with neostigmine, and salivation was most copious with carbachol. Inhalation of irritant fumes induced transient lachrymation but various spiced materials applied to the oral mucosa had no significant effect. For routine induction of lachrymation an intramuscular injection of neostigmine (0·3 mg./kg) followed after 10 min. by a similar dose of atropine, is advocated. Salivation can be successfully induced by 0·7 mg./kg. carbachol, atropine being given only when considered necessary.