Prenatal cocaine exposure alters behavioral and neurochemical sensitization to amphetamine in adult rats.
This study examined the neurochemical correlates of amphetamine (AMPH)-induced behavioral effects in prenatally saline (PSAL)-exposed or cocaine (PCOC)-exposed male rats. Pregnant Long-Evans rats received saline or saline containing cocaine hydrochloride (20 mg/kg s.c., b.i.d.) from gestational days 15-21. Animals were left with their biological mothers. Adult offspring were exposed to daily saline or AMPH (0.5, 1.5, or 5 mg/kg, i.p.) injections for 7 days. Behaviors were recorded in an open field during the first hour post-injection. PCOC rats did not exhibit behavioral anomalies during habituation to injection-stress or placement in the open field. PCOC rats displayed significant alterations in stereotyped responses to acute or intermittent exposure to various doses of AMPH. Within 48 h of the final testing day, striatal tissue was obtained from these animals and electrically-evoked [3H]acetylcholine (ACh) release was measured from striatal slices. Superfusion of tissue slices with various concentrations of AMPH (1-1000 nM) produced dose-dependent inhibition of ACh release in both PSAL and PCOC rats repeatedly injected with saline as adults. However, AMPH-induced inhibition of ACh release was decreased in PCOC rats repeatedly injected with AMPH as adults. At 5 mg/kg AMPH, PCOC rats exhibited increased mortality compared to PSAL rats. These data suggest that PCOC exposure produces long-lasting alterations in nigrostriatal transmission and behaviors mediated by this system.
Glatt
S J
SJ
Department of Psychology, Northeastern University, Boston, MA 02115, USA.
Bolaños
C A
CA
Trksak
G H
GH
Crowder-Dupont
C
C
Jackson
D
D
D000109:Acetylcholine / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects* / Q000502:physiology; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003042:Cocaine / Q000494:pharmacology; D003342:Corpus Striatum / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005220:Fathers; D005260:Female; D006120:Grooming / Q000187:drug effects; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018812:Paternal Exposure / Q000009:adverse effects; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D051381:Rats; D020318:Rats, Long-Evans
D000697:Central Nervous System Stimulants; D000661:Amphetamine; D003042:Cocaine; D000109:Acetylcholine