Dextromethorphan (DXM) is an anti-tussive compound, developed in the 1960’s found in many over the counter medications including Robitussin®.

DXM is an N-methyl-D-aspartate receptor antagonist, which at pharmacological doses produces little side effects, but at higher, recreational doses, it produces effects similar to PCP and Ketamine.

The prevalence of DXM abuse, especially among youth and young adults is on the rise (Zaiaee et al. 2005).

The research into the effect of DXM, especially at higher doses is somewhat lacking. DXM has been shown, however, to cause increases in mortality and neural tube defects in chickens at even very small doses (Andoloro et al. 1998).

Zebrafish are a convenient, inexpensive model for studying various effects of pharmacological agents on embryonic development as zebrafish embryos are small, transparent, develop outside of the body and are usually produced regularly and in large quantities.

Examine the teratogenicity and lethality of dextromethorphan (DXM) on zebrafish embryos.

Fish were bred, embryos collected and stored at 28.5oC.

Embryos were divided evenly into the wells of a multi-well plate containing increasing concentrations of DXM.

At ~24hrs post exposure (48hpf) living embryos were counted and examined for morphological defects

Methods

Concentration (mg/ml) n* Lethality

(%) Observations

15 5 10010 5 1007 5 1005 5 1003 20 100

2.4 6 1001.6 7 100.8 8 28.5 Curved tails .3 31 9.7 Increasing

responsiveness.03 26 0

.003 11 0

.0003 25 0.00003 24 0

0 31 0

Results

The Effects of Robo-Tripping on Embryonic Development Using Zebrafish

(Danio rerio) as a Model.Eric Brown, Department of Biology, York College of Pennsylvania

There appears to be a correlation between DXM exposure and embryo death.

DXM appears to have some capacity to cause morphological abnormalities in embryo development, possibly affecting reaction time.

Literature CitedAndaloro, V., Monaghan, D., Rosenquist, T., (1998)

Dextromethorphan and other n-methyl-d-aspartate receptor antagonists are teratogenic in the avian embryo model. Pediatric Research. 43(1): 1-7.

Zaiaee, V., Hamed, E.A., Hoshmand, A., Amini, H., Kebriaeizadeh, A., Sman, K., (2005) Side effects of dextromethorphan abuse, a case series. Addictive Behaviors. 30: 1607-1613

Further develop the dose-response curve between the concentrations of .3-1.6mg/ml.

Examine the effects of other n-methyl d-aspartate receptor antagonists to see if all have similar effects, and what effect they may have on gene expression.

Figure 2: Dose-Response curve of DXM on 24hpf embryos. Doses were determined in mg/ml and converted to molarity for graphing purposes. There is a marked increase in mortality between .6-1.6 mg/ml.

Figure 3: A 48hpf embryo exposed to .8mg/ml DXM for 24hrs, exhibiting curved tail (Left) A 48hpf embryo unexposed to DXM showing normal development (Right).

http://reliablesignals.blogspot.com/2010/11/we-often-think-of-depression-as-solely.html

Discussion

Further Research

Objective

Introduction

24hpf- Embryos dechorinated using 2mg/ml proteinase and dissecting probes.

AcknowledgmentsI would like to thank Dr. Hagerty for her help in constructing my graph.

Figure 1: Zebrafish breeding tanks set up to breed in the ESB.

Table 1: Concentration of DXM embryo treatments and corresponding percent mortality, as well as observations.

*: Number of embryos tested.