An Examination of the Effects of 5-Methoxy-N,N-di(iso)propyltryptamine Hydrochloride (Foxy) on Cognitive Development in Rats

Abstract

The hallucinogenic "designer drug" known as Foxy or Methoxy Foxy and formally know as 5-Methoxy-N,N-di(iso)propyltryptamine hydrochloride (5-MeO-DIPT) is rapidly gaining popularity among recreational users. However, little is known about the consequences of its use on neuropsychological development or behavior. During one of two adolescent periods, the rats were given repeated injections of either saline or 5 mg/kg of 5-MeO-DIPT. Once the animals reached 80 days of age, they were trained and tested on a number of tasks designed to assess the effects of 5-MeO-DIPT, if any, on memory tasks with spatial components that presumably involve declarative memory systems and on a nonspatial task that is considered sensitive to disruptions in nondeclarative memory. With one exception, both the 5-MeO-DIPT- and saline-treated rats were able to master the spatial navigation tests at comparable rates. However, the performance of the drug-treated rats was markedly inferior to that of the control animals on a response-learning task, suggesting a lack of flexibility in adapting their responses to changing task demands. This could indicate reductions in serotonin activity in the forebrain similar to the effects of studied drugs such as methylenedioxymethamphetamine (MDMA), suggesting 5-MeO-DIPT may act as a toxin compromising serotoninergic systems in the brain.

Electroencephalographic and Convulsive Effects of Binge Doses of (+)- Methamphetamine, 5-methoxydiisopropyltryptamine, and (±)-3,4- Methylenedioxymethamphetamine in Rats

“…Seizures and EEG abnormalities are associated with cognitive impairments [99–101]. Consistent with this, we and others have shown that rats given Foxy (30–80 mg/kg total) resulted in egocentric and spatial learning deficits following treatment [31, 60, 61]. Further research into how Foxy induces seizures is warranted given the present findings.…”

“…This experiment determined the EEG profile in rats of three popular drugs of abuse using the exact dosing regimen shown to induce learning and memory deficits [46, 47, 56, 62] and neurochemical changes consistent with those seen in chronic users upon post mortem examination [33, 35, 51, 53, 60, 61]. Both Foxy and MA resulted in altered EEG activity, with Foxy producing more severe effects.…”

“…Foxy affects the serotonergic system and most predominately the 5-HT 2A receptor [70], the 5-HT transporter [71], and 5-HT turnover [31] but does not appear to alter 5-HT, DA, or NE levels in adults rats [31]. In mice, Foxy reduces 5-HT levels in the hippocampus and prefrontal cortex [60]. MDMA affects the 5-HT system in rats [72, 73], non-human primates [74], and humans [75–77] with some effects upon DA [73, 78–81] and NE [82, 83]; however, it is primarily a dopaminergic agent in mice [84–86].…”

“…We have shown that a single dose of 20 mg/kg induces alterations in glucose and an elevated stress response during development and adulthood [59], while 2 h apart doses of 10 or 20 mg/kg/elicits elevated corticosterone and spatial learning deficits in adults [31]. Other studies, administering Foxy to adolescent rats (P35–48, 6 × 5–20 mg/kg/48 h), demonstrated spatial learning and serotonergic deficits [60, 61]. Furthermore, daily doses (4 × 10 mg/kg/2 h) during development results in long-term deficits in learning and increased anxiety [62].…”

Glucose and corticosterone changes in developing and adult rats following exposure to (±)-3,4-methylendioxymethamphetamine or 5-methoxydiisopropyltryptamine

“…Furthermore, Foxy induced an increase in the head-twitch response in mice [20]. Rats exposed to Foxy during development demonstrated deficits in response learning [13], spatial learning in the Morris water maze (MWM), and exaggerated hyperactivity following a methamphetamine challenge in adulthood [57]. …”