Question

A key understanding of how synapses work is that they must be able to 1. Turn a signal on, 2. Turn a signal off again. Explain why two neurons, one dopaminergic, one glutergic demonstrate this principle in Cocaine addition. In Nicotine addiction, the pathway is reversed, a Cholinergic neuron is followed by a Dopaminergic neuron. The same logic applies. Explain.

I am an addict. Which is my best excuse? 'It’s my genes'. 'It’s my mates'. 'It’s down-regulation of my receptors'. The excuse must be accompanied by an explanation.

Answer 1

Cocaine addiction is caused due to the reward system of the body that is induced by the dopamine neurotransmitter. The dopamine is a neurotransmitter which when released from the pre-synaptic neuron interacts with the post synaptic neuron receptor and induces the euphoric effect leading to the craving of more dopamine that can lead to addiction. Mechanism of cocaine addiction involves:

1. Activation of the D1 dopamine receptors: Cocain is a psychostimulant that increases the dopamine concentration by activating the D1 receptors (stimulates the neuron i.e turns on the signal) while inhibitng/blocking the D2 receptor (required for the reuptake of dopamine resulting in reduced dopamine concentration). This psychostimulant result in the long term change in the transporter and the receptor which results in a long term abuse/addiction.

2. Inhibition of the sodium channels: Cocaine also exert anesthetic effect by inhibiting the actively firing neurons i.e inhibits the NMDA receptors ( glutamatergic neurotransmission). They do this by blocking the voltage gated sodium channels in the peripheral neurons. This drug diffuses through the plasma membrane and enters in the cytoplasm and is protonated i.e becomes charged. This protonated cocaine form blocks the sodium channel which are in an open state (active) and hence inhibits the firing of the neurons which induces anesthesia.

Nicotine addiction: Mechanism involves:

1. Switiching on of the nicotinic cholenergic receptors: Smoking spikes the increase of nicotine into the lungs which are rapidly absorbes into the circulation. The nicotin binds to nicotinic cholinergic recptors (normally binds to acetylcholine) which results in opening of ion channelsallowing the entry of the sodium and calcium ions which further activate the release of dopamine and other neurotransmitters which induces pleasure and result in more craving of the nicotine.

2. Reduced levels of dopamine: The nicotinic cholenergic receptor (nAChR) becomes desensitized i.e inactive after being activated by nicotin which results short term tolerance against nicotin. This results in the reduced level of brain nicotin levels which leads to the resuction of dopamine and hence lead to withdrawal symptoms. This leads to more craving for nicotine.

The best excuse a drug addict can give is the downregulation of receptors. The continuous use of drug leads to the release of dopamine in large quantity that the number of D2 receptor becomes less available as compared to the neurotransmitter, this is known as downregulation. And hence the reuptake of the dopamine receptor becomes inhibited which in turn results in the long term euphoric effect. Moreover the continuous availability of dopamine also desensitizes the receptor and lead to the short term tolerance which in turn results in the withdrawal effect leading ot more craving for the drug.