Academic journal article Iranian Journal of Psychiatry

Environmental Enrichment Prevents Methamphetamine-Induced Spatial Memory Deficits and Obsessive-Compulsive Behavior in Rats

Academic journal article Iranian Journal of Psychiatry

Environmental Enrichment Prevents Methamphetamine-Induced Spatial Memory Deficits and Obsessive-Compulsive Behavior in Rats

Article excerpt

Chronic exposure to METH may produce long-term changes in the brain structure, function and synaptic plasticity (1), apoptosis (2), neurodegeneration (3) and neurotoxicity (4) in the hippocampus, these changes can affect aspects of behavior, learning and memory, and structures important for spatial learning and memory that enables an animal to recognize its position in the charted world. In this regard, it has been shown that chronic METH administration is associated with neurocognitive impairment (2), impairment of spatial working memory (5), and short- and long-term retention of a novel object recognition task (6). Our previous findings indicated that induction of methamphetamine-induced sensitization impaired spatial memory 30 and 120 minutes after injection, which persisted even after 30 days of withdrawal, but spared spatial working memory (7).

Chronic administration of METH also produces changes in mesolimbic, nigrostriatal systems and pre-frontal cortex, which then causes the rewarding effects and craving of drug (8, 9), obsessive-compulsive disorder (OCD) as stereotypy behavior (10, 11), and locomotor activity (12). Grooming behavior is an innate behavior in animals similar to obsessive-compulsive disorder (OCD) in humans (13), which is higher after chronic administration of METH (10, 11).

A recent study suggested that addictive behavior occurs following cognitive-affective mechanisms triggered by drug-related environmental cues, which in turn activate reinstatement of compulsive drug-seeking behavior (14). Thus, the reversal or prevention of METH-induced behavioral and cognitive disorders could be a useful method for the treatment of relapse after prolonged abstinence.

In our previous studies, environmental enrichment (EE) for 30 days during spontaneous METH withdrawal reduced the voluntary consumption of METH and also anxiety and depressive-like behaviors in rats.

In EE models, laboratory animals are placed in large cages with physical stimuli, including small toys and running wheel, which are much richer than the standard housing, and allow animals to explore, play and exercise; in this condition, the animal could have more control over the environment (15).

In another study in our laboratory, rats exposed to an enriched environment during induction of METH dependence showed greater decrease in behavioral withdrawal symptoms (16). In addition, the environmental enrichment could prevent spatial learning deficits induced by aging and chronic stress (17, 18), and enhance neurogenesis in the hippocampus, which is associated with improved spatial memory (19, 20). Thus, a more important question would be whether EE could blunt the deleterious effects of chronic administration of METH during METH dependence and withdrawal. Therefore, the aim of this study was to investigate whether exposure to an EE during induction of METH dependence and spontaneous withdrawal would attenuate METH-induced spatial learning and memory deficits, and OCD behavior in METH-withdrawn rats.

Materials and Method

Animals, Methamphetamine Administration and Housing Conditions

Male Wistar rats (200 ± 10 g) (n = 62) were housed at a 12-h light/dark cycle at 22-24°C temperature, with food and water ad libitum. The Methamphetamine hydrochloride (Sigma-Aldrich, M 8750) was dissolved in 0.9% saline, and the rats were chronically treated with twice-daily subcutaneous injections of METH with a dose of 2 mg/kg (sc) at 12 hours intervals, for 14 days, as described previously (15). Control rats were similarly injected with saline. Rats were placed in their home cages (standard or enriched environment) over injection period or the spontaneous withdrawal of METH. Enriched rats were placed in a large cage (96 cm x 49 cm x 38 cm) with plastic tunnels, rope, swing, balls, ramp, ladder, shelters, step, cube and a running wheel. The toys were changed every two days to maintain novelty, and control rats were placed in standard laboratory cages (42 x 34 x 15 cm) (15). …

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