Acute opioid administration induces hypothalamic-pituitary-adrenal activation and is mediated by genetic variation in interleukin (Il)1B.

There is a complex relationship between drug dependence and stress, with alcohol and other drugs of abuse both relieving stress and potentially inducing physiological stress responses in the user. Opioid drugs have been shown to modulate hypothalamic-pituitary-adrenal (HPA) activity in animal models and individual response to this modulation may play a role in continuation of drug use. Healthy young Caucasian adults were administered a single dose of immediate release oxycodone (20mg, n=30) or assigned to a control group (n=19) that was not administered the drug. At 0, 1, 2, 4 and 6h post-administration, blood and saliva samples were collected along with assessment of pupil diameter. The HPA response was determined by measurement of salivary cortisol through a commercially available enzyme-linked immunosorbent assay (ELISA). The results were compared to genotype at the -511 and -31 positions in the interleukin1B (IL1B) gene. No difference in cortisol production was initially observed between the two groups, however, when participants were separated based on their genotype for two single nucleotide polymorphisms in the promoter of the IL1B gene, which have been shown to occur at a higher frequency in opioid-dependent populations, individuals carrying the -511T and -31 C alleles (-511 C/T, -31 C/T or -511 T/T, -31 C/C) had a significantly (p<0.05) higher cortisol levels compared to individuals homozygous for the -511 C and -31T alleles. These results suggest that individuals carrying the -511T and -31 C alleles experience HPA activation in response to opioid administration and therefore may be less likely to undertake subsequent self-administration.

Antidepressant-like effects of ecstasy in subjects with a predisposition to depression.

INTRODUCTION: Positive effects of ecstasy on mood and self-esteem due to increased synaptic serotonin levels may indicate a potential antidepressant-like action. This effect may be more prominent in subjects with a pre-existing mood disturbance who may use ecstasy more frequently as a 'self-medication'. This study compared depressive symptoms and the immediate effects of ecstasy on mood in subjects with (WP) and without (NP) a predisposition to depression. METHODS: Current ecstasy users were assessed using the profile of mood states (POMS) and beck depression inventory (BDI) when drug-free, and during social gathering, when 20 subjects voluntarily consumed ecstasy (ecstasy group) and 20 abstained from ecstasy (control group). Predisposition to depression was determined using the Brief Symptom Inventory. During social gathering, POMS and BDI were administered 60 min after ecstasy consumption, or at matched time for controls. 3,4-Methylenedioxymethamphetamine (MDMA) exposure was confirmed using saliva samples collected 60 min after pill ingestion. RESULTS: There was no difference in ecstasy use patterns between the groups. When drug-free, the WP subjects had greater mood disturbance and depressive symptoms than the NP group (POMS: NP 5.85±1.63, WP 14.5±2.81, p<0.05, BDI: NP 4.9±0.86, WP 11.2±1.65, p<0.01). During social gathering, WP subjects who consumed ecstasy reported a significant decrease in depressive symptoms (F(1,35)=5.47, p<0.05). CONCLUSIONS: A decrease in depressive symptoms was observed in subjects predisposed to depression. This antidepressant-like action of MDMA may contribute to its use, particularly among people with an existing or latent depressive disorder.

Antidepressant-like effects of 3,4-methylenedioxymethamphetamine in an animal model of depression.

Increased synaptic serotonin (5-hydroxytryptamine) levels may underlie antidepressant-like effects of 3,4-methylenedioxymethamphetamine (MDMA) that may be more prominent in subjects with mood disturbance. The Flinders Sensitive Line (FSL) strain is an important animal model of depression. These rats are more immobile in the forced swimming test (FST), and their immobility is reversed by known antidepressants after prolonged administration. The objective of this study was to determine whether MDMA administration has a dose-dependent antidepressant-like effect in this animal model of depression. The effects of MDMA at 5 and 10 mg/kg following single and repeated administration were assessed in FSL rats using the FST. Sprague-Dawley rats were used as a control. During both FST sessions, saline-treated FSL rats were significantly more immobile than Sprague-Dawley rats (P<0.001). Acute MDMA administration had a dose-dependent antidepressant-like effect in FSL rats, which was most evident after 10 mg/kg. This effect was diminished after repeated administration. Methamphetamine 2 mg/kg, which was used as a positive control for locomotor activity induction, did not affect the depressive-like state in FSL rats. There were no changes in the cortical levels of 5-hydroxytryptamine and 5-hydroxyindoleacetic acid after treatments. It is concluded that MDMA exhibited an antidepressant-like effect in FSL rats, which was most evident following acute administration.

Increased effects of 3,4-methylenedioxymethamphetamine (ecstasy) in a rat model of depression.

3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) is associated with increases in core body temperature (T(C)) and depressive mood states in users. Flinders Sensitive Line (FSL) rats represent a rat model of depression originally bred from Sprague-Dawley (SD) rats. They are more sensitive to both muscarinic and serotonergic agonists and have altered thermoregulatory responses to various drugs. To examine the link between MDMA and depression, eight FSL and eight SD rats were administered saline and 5 and 7.5 mg/kg MDMA. Immediately following administration, rats were confined to an area with an ambient temperature (T(A)) of 30 ± 1°C for 30 minutes before being allowed access to a thermal gradient for four hours. The brains were removed one week after final dose of MDMA and concentrations of serotonin and dopamine were measured. Treatment with MDMA at both doses led to a higher T(C) in the FSL rats than the SD rats at high T(A) (P < 0.01). Fatalities due to hyperthermia occurred in the FSL rats after both doses, whereas all but one of the SD rats recovered well. Heart rate was also much higher after MDMA in the FSL rats throughout the experiments. The FSL rats showed significant decreases in all transmitters measured (P < 0.05). These differences between strains were not accounted for by altered blood or brain concentrations of MDMA. The results indicate that the FSL rats may be more susceptible to developing MDMA-induced hyperthermia and possible damage to the brain. These findings may be of importance to human users of MDMA who also have depression.