Distinguishing effects of cocaine IV and SC on mesoaccumbens dopamine and serotonin release with chloral hydrate anesthesia

Broderick, Patricia A.

The effect of IV 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-A(10)), 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, γ-butyrolactone (γ-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). Furthermore, the γ-BL studies indicate that cocaine's action includes a presynaptic release mechanism for the biogenic amines. Summarily, the data show that a consideration of the route of cocaine administration is crucial in determining the underlying neurochemical basis for cocaine.