Distinguishing effects of cocaine i.v. and SC on mesoaccumbens dopamineand serotonin release with chloral hydrate anesthesia.
The effect of i.v. cocaine (0.5 and 1.0 mg/kg) was studied on synaptic concentrations of dopamine (DA) and serotonin [5-hydroxytryptamine (5-HT)] in the mesoaccumbens nerve terminal, the nucleus accumbens (NAcc), in chloral hydrate-anesthetized, male Sprague-Dawley rats (Rattus norvegicus) with in vivo electrochemistry (voltammetry). In further in vivo voltammetric studies, the effects of SC cocaine on synaptic concentrations of DA and 5-HT were studied in the chloral hydrate-anesthetized paradigm in two neuroanatomic substrates, NAcc and mesoaccumbens somatodendrites, the ventral tegmental area (VTA-A10), in a dose-response fashion (10, 20, and 40 mg/kg) in six separate studies. Moreover, in two additional in vivo voltammetric studies, again using the chloral hydrate-anesthetized paradigm, the impulse flow blocker, gamma-butyrolactone (gamma-BL) (750 mg/kg, IP), was studied alone and in combination with SC cocaine (20 mg/kg) to determine whether or not cocaine can act by presynaptic releasing mechanisms for DA and 5-HT. The results show that IV cocaine concurrently and significantly increased DA and 5-HT release in the NAcc (p < 0.001, p < 0.0005, respectively) at both doses tested. Moreover, IV cocaine effects on DA and 5-HT release were significantly and positively correlated (p < 0.01). On the other hand, SC cocaine concurrently and significantly decreased DA and 5-HT release in NAcc (p < 0.0001) and VTA (p < 0.0001) at each separate dose tested. SC cocaine effects on DA and 5-HT release were significantly and positively correlated across dose and neuroanatomic substrate (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Broderick
P A
PA
Department of Pharmacology, City University of New York Medical School, NY.
D015107:4-Butyrolactone / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D002697:Chloral Hydrate; D003042:Cocaine / Q000008:administration & dosage / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism*; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D008297:Male; D008839:Microelectrodes; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D013569:Synapses / Q000187:drug effects / Q000378:metabolism
D012701:Serotonin; D002697:Chloral Hydrate; D003042:Cocaine; D015107:4-Butyrolactone; D004298:Dopamine