Elevated striatal dopamine transporters during acute cocaine abstinence as measured by [123I] beta-CIT SPECT.

OBJECTIVE: The authors examined whether striatal dopamine transporters were altered in acutely (96 hours or less) abstinent cocaine-abusing subjects, as suggested by postmortem studies. METHOD: [123I] beta-CIT and single photon emission computed tomography were used to assess striatal dopamine transporter levels in 28 cocaine-abusing subjects and 24 comparison subjects matched as a group for age and gender. RESULTS: Results showed a significant (approximately 20%) elevation in striatal V3" values in acutely abstinent cocaine-abusing subjects relative to comparison subjects. An inverse correlation between dopamine transporter level and Hamilton Depression Rating Scale score was also observed. CONCLUSIONS: These findings indicate more modest elevations in striatal dopamine transporters in cocaine-abusing subjects than noted in previous postmortem reports and suggest a possible relationship between cocaine-related depression and dopamine transporter binding.

Developmental emergence of long-term memory for sensitization in Aplysia.

Adult Aplysia exhibit both short-term and long-term memory for sensitization in the gill and siphon withdrawal reflex. Previous developmental studies showed that short-term memory for sensitization emerges late in juvenile development (stage 12; Rankin and Carew, 1988; Wright et al., 1991). In the present study, we examined the development of long-term memory for sensitization. Long-term sensitization of the siphon withdrawal reflex was quantified as an increase in mean response duration observed 20-24 h after receiving a training regime of one or more 90-min sessions of electrical shock to the tail. In the first three experiments we assessed the capacity for long-term sensitization in adults and in juveniles of stages late 12 and early 12. Animals in all three age classes showed long-term sensitization. In a fourth experiment we simultaneously trained and tested both early stage 12 animals and stage 11 animals with identical stimulus parameters that were scaled down to a level appropriate to the smaller stage 11 animals. Under these conditions, the early stage 12 animals demonstrated long-term sensitization, while the stage 11 animals still showed no evidence of long-term sensitization. These results indicate that long-term sensitization first emerges at early stage 12, which is the same developmental stage in which short-term sensitization first emerges. Although these behavioral data do not elucidate underlying mechanisms, the fact that short-term and long-term memory emerge according to the same developmental timetable is consistent with the possibility that these two forms of memory may share at least some common mechanistic features.

Cocaethylene: pharmacology, physiology and behavioral effects in humans.

Comorbid abuse of cocaine and alcohol is a common occurrence. Cocaethylene, the ethyl ester of benzoylecgonine, is an active metabolite formed as a result of simultaneous use of these substances. In humans, the concurrent ingestion of cocaine and alcohol, with resulting cocaethylene formation, has been associated with enhanced subjective euphoria, increased heart rate and increased plasma cocaine concentration. These findings suggest that cocaethylene may play a role in the morbidity and mortality associated with concurrent cocaine/alcohol abuse. This placebo-controlled, double-blinded study examined the behavioral and physiological effects and pharmacokinetics of intranasal cocaethylene administration in humans (n = 8), using cocaine as a comparator. Cocaethylene administration resulted in a euphoria similar to that produced by cocaine, although the effects differed significantly over time. Subjects were unable to distinguish between equimolar doses of cocaine and cocaethylene, although cocaethylene appeared to be eliminated more slowly than cocaine. Cardiovascular effects of cocaethylene and cocaine were similar. These findings are considered in light of the epidemiology and possible consequences of cocaine and alcohol abuse.

Delayed-onset sensitization emerges after dishabituation in developing Aplysia.

A recent study of the development of nonassociative learning in the siphon withdrawal reflex of Aplysia showed that dishabituation (facilitation of an habituated response) and sensitization (facilitation of a nonhabituated response) emerge according to different developmental timetables: dishabituation precedes sensitization by approximately 60 days (Rankin & Carew, 1988). Both forms of facilitation of the reflex were observed within 90 s of an electrical shock to the tail. However, more recent work by Marcus and colleagues (1988) in adult animals revealed that sensitization can have a delayed onset of 20-30 min after a strong tail shock. Since the developmental study of Rankin and Carew (1988) only tested the reflex for 10 min after tail shock, it is possible that sensitization was in fact present at earlier developmental stages, but was undetected. To examine this question, in the present study we utilized a longer (40-50 min) post-shock observation period to determine whether delayed-onset sensitization is exhibited in juvenile Aplysia, and if so, when it is expressed during development. In our first experiment, we found that Early Stage 12 juveniles (80-95 days after metamorphosis) showed significant delayed-onset sensitization 30-50 min after a strong tail shock. In a second experiment, we found that delayed-onset sensitization was absent in Stage 11 animals (20-70 days after metamorphosis). Thus delayed-onset sensitization emerges in Early Stage 12. The fact that the birthdate of delayed-onset sensitization is at least 30 days after that of dishabituation (Rankin & Carew, 1987, 1988) supports the hypothesis that these two forms of nonassociative learning may have at least partly different underlying mechanisms.

Alcohol plus cocaine: the whole is more than the sum of its parts.

Cocaethylene, an active metabolite that arises through hepatic transesterification of cocaine when cocaine and ethanol are used together, shares many neurochemical and pharmacological properties with cocaine. Cocaethylene is similar to cocaine in its properties as an indirect dopamine agonist, and human subjects cannot distinguish its effects from those of cocaine. Cocaethylene, and especially its isopropyl analog, are more selective indirect dopamine agonists than cocaine, with relatively weak potency at the serotonin transporter. Cocaethylene may contribute to the manifestations and consequences of combined cocaine and ethanol use, although its relative importance remains unclear.