The neural basis of drug craving: An incentive-sensitization theory of addiction

Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.

https://science.sciencemag.org/content/sci/274/5292/1527.full.pdf

Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region

Behavioural despair in rats: a new model sensitive to antidepressant treatments.

The open field as a paradigm to measure the effects of drugs on anxiety-like behaviors: a review

This study demonstrated that distinct patterns of active behaviors are produced by antidepressants that selectively inhibit norepinephrine (NE) or serotonin (5-HT) uptake in the rat forced swimming test (FST). A behavior sampling technique was developed to score the active behaviors swimming, climbing and diving, as well as immobility. The rat's behavior was recorded at the end of each 5-s period during the test session. The sampling technique was both reliable, as demonstrated by test-retest reliability and inter-rater reliability, and valid, as shown by comparison to the timing of behavior durations. Five different antidepressant drugs which block monoamine uptake and two 5-HT1A receptor agonists were shown to decrease immobility in the FST; however, they produced distinct patterns of active behaviors. The selective NE uptake inhibitors desipramine and maprotiline selectively increased climbing, whereas the selective serotonin reuptake inhibitors (SSRIs) fluoxetine, sertraline and paroxetine selectively increased swimming. The 5-HT1A receptor agonists 8-OH-DPAT and gepirone also selectively increased swimming. These results show that:1) SSRIs are not false negatives in the FST; 2) at least two behaviorally distinct processes occur in the FST; and 3) enhancement of NE neurotransmission may mediate climbing in the FST, whereas enhancement of 5-HT neurotransmission may mediate swimming.

Active behaviors in the rat forced swimming test differentially produced by serotonergic and noradrenergic antidepressants.

Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats.

Effects of MK-801 and antidepressant drugs in the forced swimming test in rats.

Hypotheses concerning the mechanism of action of antidepressant drugs.

Effect of apomorphine on motility in rats

We examined the effect of trazodone (TR), a non-tricyclic antidepressant drug with an unknown mechanism of action, as well as its supposed metabolitesβ-(3-oxo-s-triazolo-[4, 3 a]-pyridin-2-yl-propionic acid (OTPA) and 1-(m-chlorophenyl)-piperazine (CPP) on the serotonin (5-HT) system in a model of the hind limb flexor reflex of the spinal rat.

Jerzy Maj

Papers

Synergistic effect of uncompetitive NMDA receptor antagonists and antidepressant drugs in the forced swimming test in rats.

Effects of MK-801 and antidepressant drugs in the forced swimming test in rats.

Hypotheses concerning the mechanism of action of antidepressant drugs.

Effect of apomorphine on motility in rats

Trazodone, a central serotonin antagonist and agonist.