A Single Exposure to Restraint Stress Induces Behavioral and Neurochemical Sensitization to Stimulating Effects of Amphetamine

Abstract

Evidence indicates that repeated exposure to stressful events sensitizes the motor and addictive effects of drugs of abuse in rats. Regarding a single exposure to one restraint stress, previous findings have shown that it is sufficient to induce behavioral sensitization to stimulating and reinforcing properties of abuse drugs (e.g., amphetamine and morphine), as measured by locomotor activity and conditioned place preference, respectively. It is well known that enhanced dopaminergic neurotransmission in the nucleus accumbens and striatum plays a critical role in the development and/or expression of repeated stress‐induced or drug‐induced sensitization. In addition, involvement of NMDA receptors has been implicated in its development. However, whether sensitization induced by a single restraint stress exposure represents the same neurobiologic phenomenon is unknown. We studied the following issues: (a) influence of a single restraint exposure on the stimulating effects of amphetamine on dopamine release by microdialysis from striatum and (b) involvement of glutamatergic pathways, specifically those innervating striatum, on stress‐induced sensitization to amphetamine, by administering MK‐801 ip (0.1 mg/kg) or intrastriatally (1 μg/0.5 μL) previous to an acute restraint stress. For microdialysis studies (a) or intrastriatal administration of MK‐801 (b), Wistar rats (250‐330 g) were implanted stereotactically under anesthesia with a guide cannula in the striatum. After 2 days, animals were immobilized for 2 hours in a Plexiglas device. Control animals remained in their home cages. The following day we evaluated the stimulating effect of amphetamine on (a) dopamine release from striatum or (b) locomotor activity. In studies (a), dialysis probes were inserted into the guide cannula, and baseline dopamine levels were collected for 2 hours before a challenge of amphetamine (1.5 mg/kg ip). Dialysates were then collected by 3 hours. Amphetamine challenge induced a significantly higher increase in dopamine release and locomotor activity in animals previously subjected to one restraint stress exposure, relative to that observed in the no‐restraint stress group. MK‐801 administered ip or intrastriatally blocked the restraint stress‐induced sensitization to amphetamine. First, our results point out that a single restraint stress exposure is a pertinent stimulus to induce sensitization of amphetamine's stimulating effects on dopaminergic neurotransmission in the striatum. Secondly, NMDA‐glutamatergic receptors, specifically those placed in the striatum, are implicated in the development of stress restraint‐induced sensitization.

A Glutamate–Dopamine Interaction in the Persistent Enhanced Response to Amphetamine in Nucleus Accumbens Core but not Shell Following a Single Restraint Stress

“…The irregular pattern to d-AMPH observed 24 h after the stress session seems to be a characteristic response at this time point, as was shown in our previous studies (Diaz-Otañez et al, 1997;Pacchioni et al, 2002), while that observed 1 week after stress had a more regular and sustained pattern. The difference in the behavioral responses to d-AMPH after stress might be related to the clearly different d-AMPHinduced DA response underlying both the short-and the long-term stress-induced effects.…”

“…To draw a parallel between the previous findings and the microdialysis experiments, we ran the locomotor activity assay in a different group of rats, and used a new set of activity monitors. The results (Figure 1a and Pacchioni et al, 2002). Restraint stress induced a higher DA release evoked by d-AMPH in NAcc core and shell subdivisions and CPu compared with those observed after Saline injection (Figure 2).…”

“…The rats were allowed to recover for 48-72 h. were dissolved in saline immediately before use. The doses were calculated on the basis of the weight of the salt of each drug, and were chosen considering our previous works (Diaz-Otañez et al, 1997;Pacchioni et al, 2002).…”

Neuroendocrine and behavioral response to amphetamine challenge after exposure to an organophosphorus pesticide

“…Needless to say, AMPH is an indirect dopaminergic agonist and one of the most frequently abused psychostimulants. Exposure to some stressors is known to result in behavioral and neuroendocrine sensitization to AMPH [24][25][26], a state which, according to some authors, may promote the development of psychostimulant dependence and addiction [27][28]. In the context of this hypothesis, the behavioral hyposensitivity to AMPH after CVP exposure becomes intriguing.…”

Memantine: A New Mood Stabilizer for Treatment-Resistant Bipolar Disorders

“…Its stimulation is, in fact, necessary for the sensitization of amphetamine (Battisti et al, 2000;Groning et al, 2004;Ohmori et al, 1994;Pacchioni et al, 2002;Vezina & Quen, 2000;Wolf et al, 1994), methylphenidate (Gaytan et al, 2000), cocaine ( Heusner & Palmiter 2005;Li et al, 2000;Kim et al, 1996;Rompré & Bauco 2006), apomorphine (Acerbo et al, 2004;Pacchioni et al, 2002;Voikar et al, 1999) and other dopamine mimetics (Kalivas, 1995;Rockhold, 1998), nicotine (Kelsey et al, 2002), morphine (Jeziorski et al, 1994;Trujillo, 2002) and ethanol (Broadbent & Weiemier, 1999;Camarini et al, 2000;Kotlinska et al, 2006), as well as several types of stress such as, for instance, 'restraint stress' (Pacchioni et al, 2002) and 'social defeat stress' (Yap et al, 2005).…”