Estradiol enhances behavioral sensitization to cocaine and amphetamine-stimulated striatal [3H]dopamine release

Locomotor activity and stereotypy induced by cocaine is increased or 'sensitized' after repeated cocaine administration. This behavioral sensitization may be mediated by a persistent increase in dopamine (DA) transmission in mesolimbic and nigrostriatal pathways. Since the female estrous c...

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Bibliographic Details
Published in:	Brain research Vol. 566; no. 1-2; p. 255
Main Authors:	Peris, J, Decambre, N, Coleman-Hardee, M L, Simpkins, J W
Format:	Journal Article
Language:	English
Published:	Netherlands 06-12-1991
Subjects:	Amphetamine - pharmacology Animals Body Weight - drug effects Cocaine - pharmacology Corpus Striatum - drug effects Corpus Striatum - metabolism Dopamine - metabolism Drug Synergism Estradiol - blood Estradiol - pharmacology Female Male Motor Activity - drug effects Organ Size - drug effects Pituitary Gland - drug effects Progesterone - blood Progesterone - pharmacology Rats Rats, Inbred Strains Reference Values Stereotyped Behavior - drug effects Substance Withdrawal Syndrome - physiopathology Uterus - drug effects
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Summary:	Locomotor activity and stereotypy induced by cocaine is increased or 'sensitized' after repeated cocaine administration. This behavioral sensitization may be mediated by a persistent increase in dopamine (DA) transmission in mesolimbic and nigrostriatal pathways. Since the female estrous cycle and ovarian steroid hormones appear to affect both cocaine sensitization and DA transmission, studies were undertaken to determine the effects of ovarian steroids on sensitization of the behavioral responses to repeated cocaine injections and any concomitant effects on striatal DA release. Young female adult rats were ovariectomized and 2 weeks later were implanted with chronic release forms of estradiol (E), progesterone (P), both (EP) or vehicle (V). Locomotor and stereotypic behavior were rated after an initial injection of either saline or cocaine (10 mg/kg, i.p.) and after the 8th daily injection of saline or cocaine. A significant increase in both locomotor and stereotypic behaviors was seen after the first cocaine injection relative to saline-injected animals and this response was not affected by steroid treatment. Repeated injections of cocaine caused sensitization of the initial behavioral response to cocaine (i.e. an increase in stereotypic and locomotor behavior) and the degree of cocaine sensitization was greatest in group E. Steroid treatment did not affect behavior in saline-treated rats. When striatal [3H]DA release was measured in vitro 1 or 7 days after the last injection, amphetamine-stimulated release was greater in vehicle-treated rats 7 days after cocaine injections but not 1 day after injections. In contrast, release was enhanced in group E both 1 and 7 days after cocaine.
ISSN:	0006-8993
DOI:	10.1016/0006-8993(91)91706-7