Access To Cocaine Research Articles

Choline acetyltransferase activity is reduced in rat nucleus accumbens after unlimited access to self-administration of cocaine

Choline acetyltransferase (ChAT) activity was measured in discrete areas of rat brain after chronic, unlimited access to self-administration of cocaine. Mean activity of ChAT was reduced by approximately 30% in the nucleus accumbens, both on the last day of cocaine access and after 3 weeks cocaine withdrawal. These data suggest that chronic cocaine exposure might inhibit nucleus accumbens cholinergic neurones which could underlie some of the behavioral effects of cocaine.

Heterogeneous subregional binding patterns of 3H-WIN 35,428 and 3H-GBR 12,935 are differentially regulated by chronic cocaine self- administration

We examined the influence of chronic cocaine exposure, in an unlimited access self-administration paradigm, on density of the dopamine transporter (3H-WIN 35,428 and 3H-GBR 12,935 binding) and concentration of monoamine (dopamine, serotonin, noradrenaline and metabolites) neurotransmitters in rat brain. In normal rodent striatum 3H-WIN 35,428 and 3H-GBR 12,935 binding to the dopamine transporter, although generally similar, showed different subregional rostrocaudal and mediolateral gradients, suggesting that the two ligands might bind to different subtypes or states of the dopamine transporter. Following chronic, unlimited access cocaine self-administration, binding of 3H-WIN 35,428 was significantly elevated in whole nucleus accumbens (+69%, p < 0.001) and striatum (+65%, p < 0.001) on the last day of cocaine exposure ("on-cocaine group"); whereas in the 3 week withdrawn animals ("cocaine-withdrawn group"), levels were either normal (striatum) or reduced (-30%, p < 0.05, nucleus accumbens). Although similar changes in 3H-GBR 12,935 binding were observed, this dopamine transporter ligand showed a smaller and highly subregionally dependent increase in binding in striatal subdivision of the on-cocaine group, but a more marked binding reduction in the cocaine-withdrawn animals. As compared with the controls, mean dopamine levels were reduced in striatum (-15%, p < 0.05) of the on-cocaine group and in nucleus accumbens (-40%, p < 0.05) of the cocaine-withdrawn group. These data provide additional support to the hypothesis that some of the long-term effects of cocaine exposure (drug craving, depression) could be consequent to reduced nucleus accumbens dopamine function. Our data also suggest that dopamine transporter concentration, and perhaps function, might undergo up- or downregulation, either as a direct effect of cocaine, or indirectly as part of a homeostatic response to altered synaptic dopamine levels, and therefore might participate in the neuronal events underlying cocaine-induced behavioral changes.

A concurrently available nondrug reinforcer prevents the acquisition or decreases the maintenance of cocaine-reinforced behavior

Lever-pressing responses of 55 rats were reinforced with IV-delivered cocaine (0.2 mg/kg) or saline under conditions of continuous access for 15 24-h sessions. The rats also responded on tongue-operated drinking devices for deliveries of a 3% (w/v) glucose + 0.125% (w/v) saccharin (G+S) solution or water. The effects of removing these substances on behavior maintained by G+S, water, cocaine, or saline were compared in 11 groups. Terminating cocaine access produced a decrease in G+S drinking and an increase in food and water intake. In contrast, a group of rats that did not initially self-administer G+S showed increases in G+S drinking when cocaine was removed, and G+S-maintained responding persisted when cocaine was reinstated. Substitution of water for G+S produced a nearly two-fold increase in cocaine-reinforced behavior but no change in IV-delivered saline self-administration in a control group. A group that did not initially self-administer cocaine increased its infusion rate to over 400 infusions per day as soon as G+S was replaced with water. The effect of presenting cocaine to a group that responded for G+S alone was to decrease G+S intake, but there was only a transient decrease in water intake in the control group. Likewise, presentation of G+S to a group of rats self-administering cocaine resulted in a decrease in infusions, but saline infusions did not change in a control group. Generally, there was an increase in food and water intake during cocaine removal, but food and water intake did not vary systematically with the removal or presentation of G+S.(ABSTRACT TRUNCATED AT 250 WORDS)

Cocaine withdrawal produces behavioral disruptions in rats

There is currently no laboratory or clinical evidence from animal or human studies documenting a withdrawal syndrome associated with cocaine dependence, although many users report that withdrawal disturbances are responsible for their repeated use of the drug. In the present study rats self-administered i.v. cocaine and a sweetened drinking solution. When cocaine access was terminated there was a marked suppression in operant behavior reinforced by the sweetened solution, and this withdrawal disruption was immediately reversed when cocaine was reinstated. There were no physical signs of withdrawal, and food intake increased when cocaine was withdrawn. The results suggest that sensitive behavioral tests reveal aspects of drug dependence that may account for persistent abuse.

The role of food deprivation in the maintenance and reinstatement of cocaine-seeking behavior in rats

Lever-pressing responses of a group of five rats (Group E) were rewarded with i.v. injections of cocaine (0.1 mg/kg) under conditions of continuous access for eleven 24-h sessions. When the rats were partially food-deprived every third day, cocaine infusions more than doubled during that session. When saline was substituted for cocaine, responding diminished over a 10-day period (Extinction Phase), but when the rats were subsequently food-deprived every third day (Testing Phase), for a total of six cycles (20 sessions), high rates of responding for saline were reinstated only during food deprivation sessions. Seven control groups were included to investigate several questions regarding this effect. Group C-1 received cocaine but no food deprivation experience during the Training Phase, and Group C-2 received food deprivation experience without cocaine access. The results showed that simultaneous presentation of both the food deprivation condition and cocaine was necessary to reinstate food deprivation-induced increases in responding during the Testing Phase. To test for the importance of the contingency between responding and cocaine infusions during food deprivation (and satiation) in the Training phase, Group C-3 was yoked to Group E; they received the same number and pattern of infusions during the Training Phase, but infusions were not contingent upon lever-press responses. This group showed only small increases in saline-maintained responding due to food deprivation during the Testing Phase. Groups C-4 and C-5 were treated as Groups C-3 and E, respectively, except they were partially food-deprived during the 10-day Extinction Phase. Three of five rats in Group C-4 and all rats in Group C-5 showed no increases due to food deprivation during the Testing Phase. Group C-6 was pre-exposed to food deprivation before the experiment began, and Group C-7 was exposed to food deprivation only once during the Training Phase. Both procedures weakened the ability of food deprivation to produce high rates of saline-maintained responding. It was concluded that novel interoceptive stimuli related to food deprivation had become associated with the relatively novel reinforcing effects of cocaine and these interoceptive stimuli functioned as conditioned reinforcers to increase the maintenance and reinstatement of drug-seeking behavior.

Book Reviews

Journal Article Book Reviews Get access Cocaine and Other Stimulants (Advances in Behavioural Biology. Vol. 21). Eds. H. Ellingwood Everett, and M. Marlyne Kilbey. Plenum 1977. $59.40. A.H. A.H. Search for other works by this author on: Oxford Academic PubMed Google Scholar Alcohol and Alcoholism, Volume 14, Issue 3, Winter 1979, Pages 168–169, https://doi.org/10.1093/oxfordjournals.alcalc.a044184 Published: 01 December 1979