Serotonin reuptake is less efficient in taste aversion resistant than in taste aversion-prone rats.

We have previously reported the development of rat lines bred selectively for differences in taste aversion conditionability. Earlier studies demonstrated that the taste aversion resistant (TAR) animals exhibited lower concentrations of brain serotonin and consumed greater amounts of ethanol than their taste aversion prone (TAP) counterparts. In the present study, TAR rats demonstrated significantly less efficient brain serotonin transport compared to TAP rats, but the rat lines demonstrated similar levels of serotonin transporter or V(max) and similar whole brain paroxetine (a specific serotonin reuptake inhibitor) binding (B(max)). These results suggest that the rat lines differ in the mechanisms that transport serotonin into nerve endings, but do not differ in the binding of serotonin to the transporter or in the number of serotonin transport sites. The data support the hypothesis that genetically determined differences in the serotonin system contribute to individual differences in taste aversion conditionability. The findings further suggest that differences in serotonin transport may influence the propensity to self-administer ethanol.

Differences in free-choice ethanol acceptance between taste aversion-prone and taste aversion-resistant rats.

Taste aversion (TA)-prone (TAP) and TA-resistant (TAR) rats were tested for naive, nonforced acceptance of ethanol. Ethanol acceptance had played no role in line development. Rather, the lines had been developed via bidirectional, nonsibling matings based on susceptibility to develop cyclophosphamide-induced conditioned TAs to a 0.1% saccharin solution (at cyclophosphamide doses of 12.5 mg/kg for males and 15.0 mg/kg for females, i.p.). Rats from the 23rd selectively bred generations, with no prior exposure to ethanol, were given 24-hr access to a two-bottle choice between plain tap water and a solution of ethanol in water. Rats were initially given access to 1% ethanol in water, and the ethanol concentration was increased by 1% every 3 days to a maximum of 10%. Ethanol consumption (g ethanol consumed/kg body weight) and preference scores (volume ethanol solution consumed/total fluid intake) were determined by daily bottle weighings. At 1% ethanol concentration, there were no differences between the rat lines in terms of ethanol consumption or preference. At concentrations of 2 to 10%, TAP rats consumed less ethanol and showed a decreased preference for the ethanol solutions than TAR rats. Maximum ethanol consumption was reached at the 6% concentration for both lines. The mean (+/- SE) values of consumption at 6% ethanol were 1.8 (+/- 0.8) and 5.6 (+/- 0.5) g of ethanol/kg body weight for TAP and TAR rats, respectively. Mean (+/- SE) preference scores at 6% ethanol were 26 (+/- 12) and 76 (+/- 6) for TAP and TAR rats, respectively. These findings indicate that differences in TA conditionability may be associated with the propensity of rats to be high or low consumers of ethanol. Based on these data, it is hypothesized that high susceptibility for TA conditionability may deter many individuals from consuming the high levels of ethanol that usually precede alcohol tolerance and dependence.

Brain levels of amines and amino acids in taste aversion-prone and -resistant rats.

Possible biological contributions to taste aversion (TA) conditionability were explored by comparing whole-brain levels of five neurotransmitter amines and 14 common amino acids within TA-prone (TAP) and TA-resistant (TAR) rats. The selectively bred strains had been developed via 22 generations of bidirectional nonsibling matings based on susceptibility to cyclophosphamide-induced conditioned TAs. The target substances were separated by HPLC and were measured by electrochemical or fluorometric procedures. The TAP brains had higher levels of serotonin (5-HT) and lower levels of norepinephrine (NE) than TAR brains. No strain differences were found with respect to dihydroxyphenylalanine (DOPAC), dopamine (DA), or 5-hydroxyindoleacetic acid (5-HIAA). Among amino acids, TAP rats had lower levels of lysine than TARs: no other differences were detected. Therefore, higher levels of 5-HT and lower levels of NE and lysine were associated with enhanced TA conditionability. The 5-HT and NE results extend prior indications of their central neurotransmitter TA involvements. The functional role of lysine in TA or other brain functions remains obscure.

Continued development and unconditioned stimulus characterization of selectively bred lines of taste aversion prone and resistant rats.

This report updates the bidirectional selective breeding of taste aversion (TA) prone (TAP) and TA resistant (TAR) rat lines from the 8th through the 22nd generations. A palatable saccharin solution and the aversive consequences of a cyclophosphamide injection are the respective conditioned stimulus (CS) and unconditioned stimulus (US) of line development. Nonsibling matings within each of the two extremes of TA conditionability have produced TAP and TAR lines having markedly different TA propensities. As previously reported, the substitution of a rotational (i.e., motion sickness) US for cyclophosphamide during TA conditioning also produced characteristic line differences in conditioned taste aversion acquisition. The present report extends the effective line separating USs to include injections of lithium chloride, emetine hydrochloride, and EtOH. A range of EtOH dose levels produced dose-dependent TAs within TAP rats but failed to induce TAs in TAR rats. Following the conclusion of TA testing, the administration of a hypnotic EtOH dose produced equivalent loss of righting capability and equivalent hypothermia in both TAP and TAR rats. The line differences in EtOH induced TA conditionability therefore do not reflect general line differences in EtOH sensitivity. The lines may be useful within studies of biological bases of TA conditionability and animal analog studies of prevention and treatment of alcohol dependence.

Chemical aversion treatment of alcohol dependence.

Developments in the application of chemical aversion therapy to the treatment of alcohol dependence are discussed. Historical factors leading to the early use of chemical aversion therapies are delineated and the theoretical underpinnings of chemical aversion interventions are evaluated. Ethical and procedural considerations are addressed and an assessment of the efficacy of the therapy is attempted. Future research activities that would lead to refinement of chemical aversion therapy protocols are highlighted. The effectiveness of chemical aversion treatment of alcohol dependence is discussed vis-a-vis production of condition alcohol-aversion and treatment outcome.

An appraisal of chemical aversion (emetic therapy) approaches to alcoholism treatment.

More than 35,000 alcoholics have received chemical aversion (emetic therapy) in at least 75 settings worldwide since the 1930s. This consummatory aversion (CA) treatment, which pairs ethanol ingestion with emetically induced nausea, incorporates the highly efficient variety of learning known as taste aversion (TA) conditioning. The CA literature indicates that emetic therapy should induce conditioned alcohol aversions in many alcoholics. Such aversions have been widely reported by clinicians and have been confirmed by recent psychophysiological evidence. Long standing evidence of treatment effectiveness is found in the results of private hospitals which have consistently produced 1-yr abstinence rates approximating 60%. Diminished alcohol craving is a frequently reported benefit. Few experimental evaluations have been completed, as is generally the case for all alcoholism treatments, but those which used methodologically sound temporal parameters during conditioning have supported the clinical efficacy of emetic therapy. The clear need for more definitive research notwithstanding, there are compelling indications that emetic therapy is a useful component of multimodal treatment within certain alcoholic populations. However, its availability is severely limited. Many alcoholics could probably benefit from expanded treatment availability. The time is ripe for a reevaluation of resistances to the clinical use of emetic therapy alcoholism treatment.

Megamarketing strategies for health care services.

Megamarketing, as coined by Kotler (1968), is a strategic way of thinking which takes an enlarged view of the skills and resources needed to enter and operate in obstructed or protected markets. The concept of megamarketing emphasizes the mastering and coordination of economic, psychological, political, and public relation skills and suggest that organizations can take a proactive stance in shaping macroenvironmental conditions. As health care delivery is characterized by a highly regulated environment, this marketing approach has definite applications for the health care marketer.

Differences in cyclophosphamide-induced suppression of cricket predation in selectively bred strains of taste-aversion prone and resistant rats.

Cyclophosphamide-induced conditioned suppression of cricket predation was observed in taste-aversion-prone (TAP) but not in taste-aversion-resistant (TAR) rats. These TAP and TAR strains had been selectively bred for efficient or inefficient acquisition of cyclophosphamide-induced saccharin taste aversions (TAs). Equivalent preconditioning cricket predation was practiced by nonfasted subjects of both strains. TAR rats that ate crickets before a cyclophosphamide injection were thereafter voracious predators as were saline-injected and pseudoconditioning controls of both strains. However, conditioned TAP rats subsequently displayed a marked suppression of cricket predation. Predation can provide a deprivation-free and species-natural consummatory response for studies of strain differences in TA conditionability of TAP and TAR rats. In addition, the present results indicate that TAP and TAR strain differences in TA conditionability are not restricted to the saccharin solution that was the conditioned stimulus basis of prior strain development.

Separation of taste-aversion-prone and taste-aversion-resistant rats through selective breeding: implications for individual differences in conditionability and aversion-therapy alcoholism treatment.

Both rats and alcoholic humans display considerable variability in acquisition of illness-induced consummatory aversions. Differential conditionability may be a significant modulator of outcome in alcoholics who elect taste aversion (TA) approaches to abstinence facilitation. This is a report of the ongoing development of rat strains suitable for studies of biological bases of individual differences in TA conditionability. Sprague-Dawley-derived rats have been selectively bred over seven generations as strong or weak learners of a cyclophosphamide-induced saccharin aversion. Efficiency of aversion acquisition is a selectable propensity, as indicated by progressively divergent strain separation that attained significance in the second selected generation. Subjects have also been studied with respect to shock-motivated environmental avoidance (SMEA), but efficiency of SMEA performance has not been a selection factor. Results have produced an unexpected trend across generations indicative of a within-strain reversal of TA and SMEA learning efficiency. Continuation of this reversal in subsequent generations could have important implications for studies of genetic contributions to different learning capacities and for the selection of biologically appropriate noxious stimuli for aversive therapy treatments of various target problems.

A comparison of the effects of prejob training and job experience on nonprofessional telephone crisis counselors.

This study, carried out in a telephone crisis intervention program in which nonprofessional volunteer counselors received 55 hours of prejob training, isolates the effects of prejob training and on-the-job experience. Participants in the study were evaluated on several parameters including knowledge, counseling skills, acceptance of others, and dogmatism. Three groups of volunteers were measured: group 1--measured immediately before and after prejob training, group 2--measured just after prejob training, and group 3--measured after five months of telephone counseling experience. Results indicate that counselor skills and knowledge significantly increased with prejob training, but did not show further improvement as a result of five months of experience. Attitudes such as acceptance of others and dogmatism did not change either as a result of training or experience. Dogmatism was found to be inversely related to both counselor skill and knowledge.

A reconsideration of the relevance of recent animal studies for development of treatment procedures for alcoholics.

Amit and Sutherland's conclusions concerning the use of conditioned taste aversions for alcoholism treatment are critically evaluated. Their conclusion that painful electric shock is contraindicated as a basis for alcohol taste aversions is consistent with the animal and human literature which depicts nausea as a more biologically appropriate US for taste aversion formation. However, Amit and Sutherland also conclude that alcoholics will not develop illness-induced alcohol aversions because animal studies show that aversion acquisition is disrupted by preconditioning familiarity with the conditioned stimulus (CS) - flavor - or unconditioned stimulus (US) - illness. This conclusion is untenable because Amit and Sutherland only considered animal conditioning methods that differed markedly from aversion therapy practices. Other animal studies modeled after aversion therapy procedures clearly show CS and US preexposure effects to be transitory phenomena. Moreover, experimental and clinical data show humans to be quite susceptible to taste aversion formation, and that many alcoholics do form strong alcohol aversions under appropriate conditioning parameters. Additional implications of the animal literature for effective aversion therapy are explored, and the paper concludes with a discussion of covert sensitization, a promising verbal aversion therapy which has resulted in the development of strong alcohol aversions in many volunteer subjects at the Augusta Veterans Administration Medical Center.