INVESTIGADORES
CANCELA Liliana Marina
artículos
Título:
A single exposure to restraint stress induces behavioral and neurochemical sensitization to stimulating effects of amphetamine: involvement of NMDA receptors.
Autor/es:
A.M. PACCHIONI, G. GIOINO, A. ASSIS, AND L.M. CANCELA
Revista:
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES.
Editorial:
BLACKWELL PUBLISHING
Referencias:
Año: 2002 vol. 965 p. 233 - 246
ISSN:
0077-8923
Resumen:
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 g/0.5 L) previous to an acute restraint
stress. For microdialysis studies (a) or intrastriatal administration of MK-801
(b), Wistar rats (250330 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 amphetamines stimulating effectsBSTRACT: 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 g/0.5 L) previous to an acute restraint
stress. For microdialysis studies (a) or intrastriatal administration of MK-801
(b), Wistar rats (250330 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 amphetamines stimulating effectsg/0.5 L) previous to an acute restraint
stress. For microdialysis studies (a) or intrastriatal administration of MK-801
(b), Wistar rats (250330 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 amphetamines stimulating effects
Address for correspondence: Dr. Liliana M. Cancela, Departamento de Farmacología, Facultad
de Ciencias Químicas, Universidad Nacional de Córdoba, 5000 Córdoba, Argentina. Voice:
54-351-4334437; fax: 54-351-4334420.
lcancela@fcq.unc.edu.ar
on dopaminergic neurotransmission in the striatum. Secondly, NMDAglutamatergic
receptors, specifically those placed in the striatum, are implicated
in the development of stress restraint-induced sensitization.