Enhanced Vulnerability to Cocaine Self-Administration Is Associated with Elevated Impulse Activity of Midbrain Dopamine Neurons
Tóm tắt
Individual differences in responding to a novel environment predict behavioral and neurochemical responses to psychostimulant drugs. Rats with a high locomotor response to a novel environment (HRs) exhibit enhanced self-administration (SA) behavior, sensitization, and basal or drug-induced dopamine release in the nucleus accumbens compared with rats with a low response to the novel context (LRs). In this study, we determined whether such differences in vulnerability to drug addiction might be related to differences in dopamine (DA) neuron activity. Rats were divided into HRs and LRs according to their response to a novel environment and then tested for acquisition of cocaine SA. HRs rapidly acquired cocaine SA (175 μg/kg per infusion), whereas LRs did not. Differences in cocaine SA were not caused by differences in exploratory behavior or sampling because these behaviors did not differ in HRs and LRs self-administering a saline solution. In a separate experiment, we used extracellular single-unit recordings and found that HRs exhibit higher basal firing rates and bursting activity of DA neurons in the ventral tegmental area and, to a lesser extent, in the substantia nigra pars compacta. The greater activity of midbrain DA cells in HRs was accompanied by reduced sensitivity to the inhibitory effects of a DA D2-class receptor agonist, indicating possible subsensitivity of impulse-regulating DA autoreceptors. These results demonstrate that differences in the basal activity of DA neurons may be critically involved in determining individual vulnerability to drugs of abuse.
Từ khóa
Tài liệu tham khảo
Aghajanian, 1977, Pharmacological characterization of dopamine “autoreceptors” by microiontophoretic single-cell recording studies., Adv Biochem Psychopharmacol, 16, 433
Amini, 1999, Calcium dynamics underlying pacemaker-like and burst firing oscillations in midbrain dopaminergic neurons: a computational study., J Neurophysiol, 82, 2249, 10.1152/jn.1999.82.5.2249
Bjijou, 1996, Evidence for selective involvement of dopamine D1 receptors of the ventral tegmental area in the behavioral sensitization induced by intra-ventral tegmental area injections of d-amphetamine., J Pharmacol Exp Ther, 277, 1177
Bonci, 1996, A common mechanism mediates long-term changes in synaptic transmission after chronic cocaine and morphine., Neuron, 6, 631, 10.1016/S0896-6273(00)80082-3
Brodie, 1996, Serotonin potentiates dopamine inhibition of ventral tegmental area neurons in vitro., J Neurophysiol, 76, 2077, 10.1152/jn.1996.76.3.2077
Bunney, 1973, Dopaminergic neurons: effect of antipsychotic drugs and amphetamine on single cell activity., J Pharmacol Exp Ther, 185, 560
Bunney BS Sesack SR Silva NL (1987) Midbrain dopaminergic systems: neurophysiology and electrophysiological pharmacology. in Psychopharmacology: the third generation of progress, ed Meltzer HY (Raven, New York), pp 113–126.
Cameron, 1995, Opposing roles for dopamine and serotonin at presynaptic receptors in the ventral tegmental area., Clin Exp Pharmacol Physiol, 22, 841, 10.1111/j.1440-1681.1995.tb01947.x
Deroche, 1995, Individual differences in cocaine self-administration: dose-response and ratio-response study., Soc Neurosci Abstr, 21, 767.9
Exner, 1993, Behavior in the novel environment predicts responsiveness to d-amphetamine in the rat: a multivariate approach., Behav Pharmacol, 4, 47
Henry, 1989, Electrophysiological effects of cocaine in the mesoaccumbens dopamine system: repeated administration., J Pharmacol Exp Ther, 251, 833
Koob, 1998, Circuits, drugs, and drug addiction., Adv Pharmacol, 42, 978, 10.1016/S1054-3589(08)60910-2
O'Brien CP Ehrman RN Terns JN (1986) Classical conditioning in human opioid dependence. in Behavioral analysis of drug dependence, eds Goldberg SR Stolerman IP (Academic, London), pp 329–365.
Paxinos G Watson C (1986) The rat brain in stereotaxic coordinates. (Academic, New York).
Perugini, 1994, Amphetamine administered to the ventral tegmental area sensitizes rats to the locomotor effects of nucleus accumbens amphetamine., J Pharmacol Exp Ther, 270, 690
Piazza, 1990, Individual reactivity to novelty predicts probability of amphetamine self-administration., Behav Pharmacol, 1, 339, 10.1097/00008877-199000140-00007
Roth, 1979, Dopamine autoreceptors: pharmacology, function and comparison with post-synaptic dopamine receptors., Commun Psychopharmacol, 3, 429
White, 1984, Pharmacological characterization of dopamine autoreceptors in the rat ventral tegmental area: microiontophoretic studies., J Pharmacol Exp Ther, 231, 275
Wolf, 1993, Differential development of autoreceptor subsensitivity and enhanced dopamine release during amphetamine sensitization., J Pharmacol Exp Ther, 264, 249